Aging Cell via MedWorm.com

Genes and behavior interact to determine mortality in mice when food is scarce and competition fierce

Aging Cell — Thu, 18 Mar 2010 00:00:00 +0100

(Source: Aging Cell)

Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress

Aging Cell — Wed, 17 Mar 2010 00:00:00 +0100

To determine if short-term calorie restriction reverses vascular endothelial dysfunction in old mice, old (O, n = 30) and young (Y, n = 10) male B6D2F1 mice were fed ad libitum (AL) or calorie restricted (CR, approximately 30%) for 8 weeks. Ex vivo carotid artery endothelium-dependent dilation (EDD) was impaired in old ad libitum (OAL) vs. young ad libitum (YAL) (74 ± 5 vs. 95 ± 2% of maximum dilation, P < 0.05), whereas old calorie-restricted (OCR) and YCR did not differ (96 ± 1 vs. 94 ± 3%). Impaired EDD in OAL was mediated by reduced nitric oxide (NO) bioavailability associated with decreased endothelial NO synthase expression (aorta) (P < 0.05), both of which were restored in OCR. Nitrotyrosine, a cellular marker of oxidant modification, was markedly elevated in OAL (P < 0.05), whe...

Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster

Aging Cell — Sat, 06 Mar 2010 00:00:00 +0100

Dietary restriction extends lifespan in a wide variety of animals, including Drosophila, but its relationship to functional and cognitive aging is unclear. Here, we study the effects of dietary yeast content on fly performance in an aversive learning task (association between odor and mechanical shock). Learning performance declined at old age, but 50-day-old dietary-restricted flies learned as poorly as equal-aged flies maintained on yeast-rich diet, even though the former lived on average 9 days (14%) longer. Furthermore, at the middle age of 21 days, flies on low-yeast diets showed poorer short-term (5 min) memory than flies on rich diet. In contrast, dietary restriction enhanced 60-min memory of young (5 days old) flies. Thus, while dietary restriction had complex effects on learning p...

Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

Aging Cell — Fri, 12 Feb 2010 00:00:00 +0100

Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle because of the shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution owing to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3[ndash]6 months of age, resembling the...

Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice

Aging Cell — Tue, 02 Feb 2010 00:00:00 +0100

We report that aging in C57BL/6 mice was associated with an increase in adrenal production of glucocorticoids as well as bone expression of 11[beta]-hydroxysteroid dehydrogenase (11[beta]-HSD) type 1, the enzyme that activates glucocorticoids. Aging also decreased the volume of the bone vasculature and solute transport from the peripheral circulation to the lacunar-canalicular system. The same changes were reproduced by pharmacologic hyperglucocorticoidism. Furthermore, mice in which osteoblasts and osteocytes were shielded from glucocorticoids via cell-specific transgenic expression of 11[beta]-HSD type 2, the enzyme that inactivates glucocorticoids, were protected from the adverse effects of aging on osteoblast and osteocyte apoptosis, bone formation rate and microarchitecture, crystalli...

Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-δ

Aging Cell — Sat, 30 Jan 2010 00:00:00 +0100

A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A subpopulation of astrocytes in the SVZ specifically expresses an assembly-compromised isoform of the intermediate filament protein glial fibrillary acidic protein (GFAP-[delta]). To further define the phenotype of these GFAP-[delta] expressing cells and to determine whether these cells are present throughout the human subventricular neurogenic system, we analysed SVZ, RMS and OB sections of 14 aged brain donors (ages 74-93). GFAP-[delta] was expressed in the SVZ along the ventricle, in the RMS and in the O...

SIRT6 protects against pathological damage caused by diet-induced obesity

Aging Cell — Wed, 20 Jan 2010 00:00:00 +0100

The NAD+-dependent SIRT6 deacetylase is a therapeutic candidate against the emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in premature aging phenotypes and metabolic defects, was implicated in a calorie restriction response that showed an opposite set of phenotypes from the metabolic syndrome. To explore the role of SIRT6 in metabolic stress, wild type and transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison to their wild-type littermates, SIRT6 TG mice accumulated significantly less visceral fat, LDL-cholesterol, and triglycerides. TG mice displayed enhanced glucose tolerance along with increased glucose-stimulated insulin secretion. Gene expression analysis of adipose tissue revealed that the positive effect of SIRT6 overexpres...

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection

Aging Cell — Thu, 07 Jan 2010 00:00:00 +0100

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked A[beta] peptide. We utilized transgenic nematodes that express human A[beta] and found that late life IIS reduction efficiently protects from A[beta] toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activitie...

Insights from comparative analyses of aging in birds and mammals

Aging Cell — Wed, 23 Dec 2009 00:00:00 +0100

Many laboratory models used in aging research are inappropriate for understanding senescence in mammals, including humans, because of fundamental differences in life history, maintenance in artificial environments, and selection for early aging and high reproductive rate. Comparative studies of senescence in birds and mammals reveal a broad range in rates of aging among a variety of taxa with similar physiology and patterns of development. These comparisons suggest that senescence is a shared property of all vertebrates with determinate growth, that the rate of senescence has been modified by evolution in response to the potential life span allowed by extrinsic mortality factors, and that most variation among species in the rate of senescence is independent of commonly ascribed causes of a...

Neuroprotective effects of hydrogen sulfide on Parkinson's disease rat models

Aging Cell — Wed, 23 Dec 2009 00:00:00 +0100

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN). The present study was designed to examine the therapeutic effect of hydrogen sulfide (H2S, a novel biological gas) on PD. The endogenous H2S level was markedly reduced in the SN in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Systemic administration of NaHS (an H2S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine-hydroxylase positive neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD model. H2S specifically inhibited 6-OHDA evoked NADPH oxidase activation and oxygen consumption. Similarly, administration of NaHS also prevented the development of PD ind...

Generation of pluripotent stem cells from eggs of aging mice

Aging Cell — Tue, 08 Dec 2009 00:00:00 +0100

Oocytes can reprogram genomes to form embryonic stem (ES) cells. Although ES cells largely escape senescence, oocytes themselves do senesce in the ovaries of most mammals. It remains to be determined whether ES cells can be established using eggs from old females, which exhibit reproductive senescence. We attempted to produce pluripotent stem cell lines from artificial activation of eggs (also called pES) from reproductive aged mice, to determine whether maternal aging affects pES cell production and pluripotency. We show that pES cell lines were generated with high efficiency from reproductive aged (old) mice, although parthenogenetic embryos from these mice produced fewer ES clones by initial two passages. Further, pES cell lines generated from old mice showed telomere length, expression...

Neurodegeneration in an Aβ-induced model of Alzheimer's disease: the role of Cdk5

Aging Cell — Tue, 01 Dec 2009 00:00:00 +0100

In this study we aimed to determine the role of Cdk5 in neuronal injury occurring in an AD mouse model obtained through the intracerebroventricular (icv) injection of the A[beta]1[ndash]40 synthetic peptide. In mice icv-injected with A[beta], Cdk5 activator p35 is cleaved by calpains, leading to p25 formation and Cdk5 overactivation. Subsequently, there was an increase in tau hyperphosphorylation, as well as decreased levels of synaptic markers. Cell cycle reactivation and a significant neuronal loss were also observed. These neurotoxic events in A[beta]-injected mice were prevented by blocking calpain activation with MDL28170, which was administered intraperitoneally (ip). As MDL prevents p35 cleavage and subsequent Cdk5 overactivation, it is likely that this kinase is involved in tau hyp...

DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells

Aging Cell — Fri, 06 Nov 2009 00:00:00 +0100

In this study, we have analyzed DNA methylation changes upon long-term culture of MSC by using the HumanMethylation27 BeadChip microarray assessing 27 578 unique CpG sites. Furthermore, we have compared MSC from young and elderly donors. Overall, methylation patterns were maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Many of these differences were observed in homeobox genes and genes involved in cell differentiation. Methylation changes were verified by pyrosequencing after bisulfite conversion and compared to gene expression data. Notably, methylation changes in MSC were overlapping in long-term culture and aging in vivo. This supports the notion that replicative senescence and aging represent developmental p...

Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts

Aging Cell — Fri, 30 Oct 2009 00:00:00 +0100

Mitochondrial DNA (mtDNA) mutations are a cause of human disease and are proposed to have a role in human aging. Clonally expanded mtDNA point mutations have been detected in replicating tissues and have been shown to cause respiratory chain (RC) defects. The effect of these mutations on other cellular functions has not been established. Here, we investigate the consequences of RC deficiency on human colonic epithelial stem cells and their progeny in elderly individuals. We show for the first time in aging human tissue that RC deficiency attenuates cell proliferation and increases apoptosis in the progeny of RC deficient stem cells, leading to decreased crypt cell population. (Source: Aging Cell)

The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women

Aging Cell — Fri, 30 Oct 2009 00:00:00 +0100

Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age-associated decline in growth hormone (GH), insulin-like growth factor (IGF)-1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty-three young (36.8 ± 1.0 years), overweight (BMI 27.8 ± 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min ...

MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging

Aging Cell — Fri, 30 Oct 2009 00:00:00 +0100

The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the post-transcriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA (miRNA) microarray screening to identify dwarf-specific lead miRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature miRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveals that dwarf mice post-transcriptionally regulate key proteins o...

Caenorhabditis elegans PI3K mutants reveal novel genes underlying exceptional stress resistance and lifespan

Aging Cell — Thu, 29 Oct 2009 00:00:00 +0100

Two age-1 nonsense mutants, truncating the class-I phosphatidylinositol 3-kinase catalytic subunit (PI3KCS) before its kinase domain, confer extraordinary longevity and stress-resistance to Caenorhabditis elegans. These traits, unique to second-generation homozygotes, are blunted at the first generation and are largely reversed by additional mutations to DAF-16/FOXO, a transcription factor downstream of AGE-1 in insulin-like signaling. The strong age-1 alleles (mg44, m333) were compared with the weaker hx546 allele on expression microarrays, testing four independent cohorts of each allele. Among 276 genes with significantly differential expression, 92% showed fewer transcripts in adults carrying strong age-1 alleles rather than hx546. This proportion is significantly greater than the sligh...

Exploring mechanisms of sex differences in longevity: lifetime ovary exposure and exceptional longevity in dogs

Aging Cell — Tue, 27 Oct 2009 00:00:00 +0100

To move closer to understanding the mechanistic underpinnings of sex differences in human longevity, we studied pet dogs to determine whether lifetime duration of ovary exposure was associated with exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, age at death, and cause of death for a cohort of canine 'centenarians'[ndash] exceptionally long-lived Rottweiler dogs that lived more than 30% longer than average life expectancy for the breed. Sex and lifetime ovary exposure in the oldest-old Rottweilers (age at death, [ge] 13 years) were compared to a cohort of Rottweilers that had usual longevity (age at death, 8.0[ndash]10.8 years). Like women, female dogs were more likely than males to achieve exceptional longevity (OR, 95% CI = 2.0, 1...

Hot topics in aging research: protein translation, 2009

Aging Cell — Fri, 16 Oct 2009 23:00:00 +0100

In the last few years, links between regulation of mRNA translation and aging have been firmly established in invertebrate model organisms. This year, a possible relationship between mRNA translation and aging in mammals has been established with the report that rapamycin increases lifespan in mice. Other significant findings have connected translation control with other known longevity pathways and provided fodder for mechanistic hypotheses. Here, we summarize advances in this emerging field and raise questions for future studies. (Source: Aging Cell)

Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin

Aging Cell — Thu, 08 Oct 2009 00:00:00 +0100

Skin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during hair cycles, and repair skin epithelia following injury. As natural aging is associated with decreased skin repair capacity in humans, we have investigated the impact of age on human scalp HF bulge cell number and function. Here, we isolated human bulge cells, characterized as CD200+/KRT15+/KRT19+ cells of the HF, by dissection-combined CD200 selection in young and aged human skin. Targeted transcriptional profiling indicates that KRT15, KRT19, Dkk3, Dkk4, Tcf3, S100A4, Gas1, EGFR and CTGF/CCN2 are also preferentially expressed by human bulge cells, compared to differentiated HF keratinocytes (KC). Our results demonstrate that aging does not alter expression or localization of these HF SC markers. In addition...

Calorie restriction effects on silencing and recombination at the yeast rDNA

Aging Cell — Tue, 06 Oct 2009 23:00:00 +0100

Aging research has developed rapidly over the past decade, identifying individual genes and molecular mechanisms of the aging process through the use of model organisms and high throughput technologies. Calorie restriction (CR) is the most widely researched environmental manipulation that extends lifespan. Activation of the NAD+-dependent protein deacetylase Sir2 (Silent Information Regulator 2) has been proposed to mediate the beneficial effects of CR in the budding yeast Saccharomyces cerevisiae, as well as other organisms. Here, we show that in contrast to previous reports, Sir2 is not stimulated by CR to strengthen silencing of multiple reporter genes in the rDNA of S. cerevisiae. CR does modestly reduce the frequency of rDNA recombination, although in a SIR2-independent manner. CR-med...

Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway

Aging Cell — Wed, 30 Sep 2009 00:00:00 +0100

We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction. (Source: Aging Cell)

Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses

Aging Cell — Thu, 24 Sep 2009 23:00:00 +0100

Muscle stem (satellite) cells are relatively resistant to cell-autonomous aging. Instead, their endogenous signaling profile and regenerative capacity is strongly influenced by the aged P-Smad3, differentiated niche, and by the aged circulation. With respect to muscle fibers, we previously established that a shift from active Notch to excessive transforming growth factor-beta (TGF-[beta]) induces CDK inhibitors in satellite cells, thereby interfering with productive myogenic responses. In contrast, the systemic inhibitor of muscle repair, elevated in old sera, was suggested to be Wnt. Here, we examined the age-dependent myogenic activity of sera TGF-[beta]1, and its potential cross-talk with systemic Wnt. We found that sera TGF-[beta]1 becomes elevated within aged humans and mice, while sy...

Ambient temperature influences aging in an annual fish (Nothobranchius rachovii)

Aging Cell — Thu, 24 Sep 2009 00:00:00 +0100

In this study, we examined the survivorship and the aging process of the annual fish (Nothobranchius rachovii) reared under high (30 °C), moderate (25 °C) and low (20 °C) ambient temperatures. The results showed that low ambient temperatures prolong survivorship, whereas high ambient temperatures shorten survivorship. At low ambient temperature, expression of senescence-associated [beta]-galactosidase, lipofuscin, reactive oxygen species, lipid peroxidation, protein oxidation, mitochondrial density and ADP/ATP ratio were reduced compared with those reared at high and moderate temperatures, whereas catalase activity, Mn-superoxide dismutase activities, mitochondrial membrane potential and the levels of ATP, ADP, Sirt1 and Forkhead box O expression were elevated. The expression levels of ...

Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging

Aging Cell — Thu, 17 Sep 2009 23:00:00 +0100

Generations of biogerontologists have been puzzled by the marked intraspecific variations in lifespan of their experimental model organisms despite all efforts to control both genotype and environment. The most cogent example comes from life table studies of wild-type Caenorhabditis elegans when grown in suspension cultures using axenic media. While nuclear and mitochondrial somatic mutations and 'thermodynamic noise' likely contribute to such lifespan variegations, I raise an additional hypothetical mechanism, one that may have evolved as a mechanism of phenotypic variation which could have preceded the evolution of meiotic recombination. I suggest that random changes in cellular gene expression (cellular epigenetic gambling or bet hedging) evolved as an adaptive mechanism to ensure survi...

Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans

Aging Cell — Thu, 10 Sep 2009 23:00:00 +0100

The methionine sulfoxide reductase system has been implicated in aging and protection against oxidative stress. This conserved system reverses the oxidation of methionine residues within proteins. We analyzed one of the components of this system, the methionine sulfoxide reductase A gene, in Caenorhabditis elegans. We found that the msra-1 gene is expressed in most tissues, particularly in the intestine and the nervous system. Worms carrying a deletion of the msra-1 gene are more sensitive to oxidative stress, show chemotaxis and locomotory defects, and a 30% decrease in median survival. We established that msra-1 expression decreases during aging and is regulated by the DAF-16/FOXO3a transcription factor. The absence of this enzyme decreases median survival and affects oxidative stress re...

Dysfunction of the unfolded protein response increases neurodegeneration in aged rat hippocampus following proteasome inhibition

Aging Cell — Thu, 10 Sep 2009 23:00:00 +0100

We examined in young and aged rat hippocampus the activation of the unfolded protein response (UPR) under cellular stress induced by proteasome inhibition. Lactacystin injection blocked proteasome activity in young and aged animals in a similar extent and increased the amount of ubiquitinated proteins. Young animals activated the three UPR arms, IRE1[alpha], ATF6[alpha] and PERK, whereas aged rats failed to induce the IRE1[alpha] and ATF6[alpha] pathways. In consequence, aged animals did not induce the expression of pro-survival factors (chaperones, Bcl-XL and Bcl-2), displayed a more sustained expression of pro-apoptotic markers (CHOP, Bax, Bak and JKN), an increased caspase-3 processing. At the cellular level, proteasome inhibition induced neuronal damage in young and aged animals as ass...

Mortality shifts in Caenorhabditis elegans: remembrance of conditions past

Aging Cell — Thu, 10 Sep 2009 23:00:00 +0100

The analysis of age-specific mortality can yield insights into how anti-aging interventions operate that cannot be matched by simple assessment of longevity. Mortality, as opposed to longevity, can be used to assess the effects of an anti-aging intervention on a daily basis, rather than only after most animals have died. Various gerontogene mutations in Caenorhabditis elegans have been shown to increase longevity as much as tenfold and to decrease mortality at some ages even more. Environmental alterations, such as reduced food intake (dietary restriction) and lower temperature also result in reduced mortality soon after the intervention. Here, we ask how soon anti-aging interventions, applied during adult life, affect age-specific mortality in nematodes. Using maximum likelihood analysis,...

The efficiency of mitochondrial electron transport chain is increased in the long-lived mrg19 Saccharomyces cerevisiae

Aging Cell — Tue, 01 Sep 2009 23:00:00 +0100

In this study, we provide evidence for the existence of an alternative pathway to explain the observed higher mitochondrial efficiency in the long-lived mrg19 mutant of Saccharomyces cerevisiae. Although we observe similar amounts of mitochondria in mrg19 and wild-type (wt) yeast, we find that mrg19 mitochondria have higher expression of ETC components per mitochondria in comparison with the wt. These findings demonstrate that more efficient mitochondria because of increased ETC per mitochondria can also produce less mtROS. Taken together, our findings provide evidence for an alternative explanation for the involvement of higher mitochondrial activity in prolonging lifespan. We anticipate that similar mechanisms might also exist in eukaryotes including human. (Source: Aging Cell)

Calorie restriction reduces rDNA recombination independently of rDNA silencing

Aging Cell — Tue, 01 Sep 2009 23:00:00 +0100

Calorie restriction (CR) extends lifespan in yeast, worms, flies and mammals, suggesting that it acts via a conserved mechanism. In yeast, activation of the NAD-dependent histone deacetylase, Sir2, by CR is thought to increase silencing at the ribosomal DNA, thereby reducing the recombination-induced generation of extrachromosomal rDNA circles, hence increasing replicative lifespan. Although accumulation of extrachromosomal rDNA circles is specific to yeast aging, it is thought that Sirtuin activation represents a conserved longevity mechanism through which the beneficial effects of CR are mediated in various species. We show here that growing yeast on 0.05 or 0.5% glucose (severe and moderate CR, respectively) does not increase silencing at either sub-telomeric or rDNA loci compared with ...

Effects of myostatin deletion in aging mice

Aging Cell — Sun, 30 Aug 2009 23:00:00 +0100

Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knock-out (KO) mouse studies suggest myostatin also affects adiposity, glucose handling and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (Morissette et al., 2006), a concern because of cardiac hypertrophy is associated with adverse clinical outcomes. Therefore, we examined the systemic and cardiac effects of myostatin deletion in aged mice (27[ndash]30 months old). Heart mass increased comparably in both wild-type (WT) and KO mice. Aged KO mice maintained twice as much quadriceps mass as aged WT; however, both groups lost the same percentage (36%)...

Quantification of mitochondrial DNA mutation load

Aging Cell — Wed, 12 Aug 2009 23:00:00 +0100

Mitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild-type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post-PCR cloning, single-molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures...

d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila

Aging Cell — Thu, 06 Aug 2009 23:00:00 +0100

dTOR (target of rapamycin) and dFoxo respond to changes in the nutritional environment to induce a broad range of responses in multiple tissue types. Both dTOR and dFoxo have been demonstrated to control the rate of age-related decline in cardiac function. Here, we show that the Eif4e-binding protein (d4eBP) is sufficient to protect long-term cardiac function against age-related decline and that up-regulation of dEif4e is sufficient to recapitulate the effects of high dTOR or insulin signaling. We also provide evidence that d4eBP acts tissue-autonomously and downstream of dTOR and dFoxo in the myocardium, where it enhances cardiac stress resistance and maintains normal heart rate and myogenic rhythm. Another effector of dTOR and insulin signaling, dS6K, may influence cardiac aging nonauton...

Increased CaVβ1a expression with aging contributes to skeletal muscle weakness

Aging Cell — Tue, 04 Aug 2009 23:00:00 +0100

Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation[ndash]contraction (E-C) coupling. Excitation[ndash]contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation[ndash]contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel [alpha]1s (CaV1.1) and [beta]1a (CaV[beta]1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaV[beta]1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaV[beta]1a expression over the full...

Aging-dependent upregulation of IL-23p19 gene expression in dendritic cells is associated with differential transcription factor binding and histone modifications

Aging Cell — Sun, 02 Aug 2009 23:00:00 +0100

Age-associated changes in immune response increase the risk of infection and promote inflammation and autoimmunity in older adults. The newly discovered cytokine IL-23 contributes to the maintenance and expansion of Th-17 cells, which promote proinflammatory responses. Our preliminary findings suggested that Th-17 responses are increased in aged mice. IL-23 consists of p40 and p19 subunits. Expression of the p19 subunit is regulated at the transcriptional level by NF-[kappa]B p65 and c-Rel transcription factors. Using bone-marrow-derived dendritic cells (DCs) from C57BL/6 mice, we show that IL-23 protein production and p19 subunit mRNA levels are significantly increased in DCs from aged mice after activation with TLR ligands (LPS + R848) when compared with DCs of young adult mice. We found...

Calorie restriction alters mitochondrial protein acetylation

Aging Cell — Wed, 29 Jul 2009 23:00:00 +0100

Calorie restriction (CR) increases lifespan in organisms ranging from budding yeast through mammals. Mitochondrial adaptation represents a key component of the response to CR. Molecular mechanisms underlying this adaptation are largely unknown. Here we show that lysine acetylation of mitochondrial proteins is altered during CR in a tissue-specific fashion. Via large-scale mass spectrometry screening, we identify 72 candidate proteins involved in a variety of metabolic pathways with altered acetylation during CR. Mitochondrial acetylation changes may play an important role in the pro-longevity CR response. (Source: Aging Cell)

Some highlights of research on aging with invertebrates, 2009

Aging Cell — Thu, 23 Jul 2009 23:00:00 +0100

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans. Chemosensation of diffusible substances from bacteria has been shown to limit lifespan in C. elegans, while a systematic study of the different methods used to implement dietary restriction in the worm has shown that t...

Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni)

Aging Cell — Tue, 14 Jul 2009 23:00:00 +0100

Caloric restriction (CR) has been widely accepted as a mechanism explaining increased lifespan (LS) in organisms subjected to dietary restriction (DR), but recent studies investigating the role of nutrients have challenged the role of CR in extending longevity. Fuelling this debate is the difficulty in experimentally disentangling CR and nutrient effects due to compensatory feeding (CF) behaviour. We quantified CF by measuring the volume of solution imbibed and determined how calories and nutrients influenced LS and fecundity in unmated females of the Queensland fruit fly, Bactocera tryoni (Diptera: Tephritidae). We restricted flies to one of 28 diets varying in carbohydrate:protein (C:P) ratios and concentrations. On imbalanced diets, flies overcame dietary dilutions, consuming similar ca...

Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf

Aging Cell — Thu, 02 Jul 2009 23:00:00 +0100

Studies in model organisms have identified regulatory processes that profoundly influence aging, many of which modulate resistance against environmental or metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Phase 2 enzymes defend against oxygen radicals and conjugate electrophiles that are produced by Phase 1 detoxification enzymes, which metabolize lipophilic compounds. Here, we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress[ndash]response conditions. Under nonstressed conditions SKN-1 upregulate...

Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans

Aging Cell — Wed, 24 Jun 2009 23:00:00 +0100

G-proteins, including GPA-3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)-mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific defi...

Nicotinamide enhances mitochondria quality through autophagy activation in human cells

Aging Cell — Fri, 05 Jun 2009 04:00:00 +0100

Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential ([Delta][Psi]m) by accelerating autophagic degradation of mitochondria. In the NAM-treated cells, the level of LC3-II as well as the number of LC3 puncta and lysosomes co-localizing with mitochondria substantially increased. Furthermore, in the NAM-treated cells, the levels of Fis1, Drp1, and Mfn1, proteins that regulate mitochondrial fission and fusion, increased and mitochondria experienced dramatic changes in structure from filaments to dots or rings. This structural change...

The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer

Aging Cell — Mon, 01 Jun 2009 04:00:00 +0100

This study found no statistically significant association between leukocyte telomere length and advanced prostate cancer risk. However, correlations of telomere length with healthy lifestyles were noted, suggesting the role of these factors in telomere biology maintenance and potentially impacting overall health status. (Source: Aging Cell)

p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress

Aging Cell — Sun, 31 May 2009 04:00:00 +0100

In this study, we show that the C. elegans p53 ortholog cep-1 mediates these opposite effects. We found that cep-1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin [ndash] the protein defective in patients with Friedreich's Ataxia. Importantly, we show that cep-1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial-associated diseases. (Source: Aging Cell)

The low abundance of clonally expanded mitochondrial DNA point mutations in aged substantia nigra neurons

Aging Cell — Sat, 30 May 2009 23:00:00 +0100

Clonally expanded mitochondrial DNA (mtDNA) deletions accumulate with age in human substantia nigra (SN) and high levels cause respiratory chain deficiency. In other human tissues, mtDNA point mutations clonally expand with age. Here, the abundance of mtDNA point mutations within single SN neurons from aged controls was investigated. From 31 single cytochrome c oxidase normal SN neurons, only one clonally expanded mtDNA point mutation was identified, suggesting in these neurons mtDNA point mutations occur rarely, whereas mtDNA deletions are frequently observed. This contrasts observations in mitotic tissues and suggests that different forms of mtDNA maintenance may exist in these two cell types. (Source: Aging Cell)

Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging

Aging Cell — Thu, 21 May 2009 23:00:00 +0100

Expression of the p16INK4a tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16INK4a expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16INK4a expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16INK4a, but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16...

Aging alters PPARγ in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1

Aging Cell — Thu, 21 May 2009 23:00:00 +0100

Age is an important risk factor for the development of metabolic diseases (e.g. obesity, diabetes and atherosclerosis). Yet, little is known about the molecular mechanisms occurring upon aging that affect energy metabolism. Although visceral white adipose tissue (vWAT) is known for its key impact on metabolism, recent studies have indicated it could also be a key regulator of lifespan, suggesting that it can serve as a node for age-associated fat accretion. Here we show that aging triggers changes in the transcriptional milieu of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR[gamma]) in vWAT, which leads to a modified potential for transactivation of target genes upon ligand treatment. We found that in vWAT of mice, rats and men, aging induced a specific decrea...

Lifespan extension in genetically modified mice

Aging Cell — Thu, 21 May 2009 23:00:00 +0100

Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task. Lifespan studies in mice are resource intensive, requiring up to 4 years to complete. Therefore, it is critical that a set of scientifically-based criteria be followed to assure reliable results and establish statistically significant findings so other...

Reduced expression of alpha-1,2-mannosidase I extends lifespan in Drosophila melanogaster and Caenorhabditis elegans

Aging Cell — Mon, 11 May 2009 04:00:00 +0100

Exposure to sub-lethal levels of stress, or hormesis, was a means to induce longevity. By screening for mutations that enhance resistance to multiple stresses, we identified multiple alleles of alpha-1,2-mannosidase I (mas1) which, in addition to promoting stress resistance, also extended longevity. Longevity enhancement is also observed when mas1 expression is reduced via RNA interference in both Drosophila melanogaster and Caenorhabditis elegans. The screen also identified Edem1 (Edm1), a gene downstream of mas1, as a modulator of lifespan. As double mutants for both mas1 and Edm1 showed no additional longevity enhancement, it appeared that both mutations function within a common pathway to extend lifespan. Molecular analysis of these mutants revealed that the expression of BiP, a putati...

Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae

Aging Cell — Thu, 30 Apr 2009 04:00:00 +0100

Following cessation of growth, yeast cells remain viable in a nondividing state for a period of time known as the chronological lifespan (CLS). Autophagy is a degradative process responsible for amino acid recycling in response to nitrogen starvation and amino acid limitation. We have investigated the role of autophagy during chronological aging of yeast grown in glucose minimal media containing different supplemental essential and nonessential amino acids. Deletion of ATG1 or ATG7, both of which are required for autophagy, reduced CLS, whereas deletion of ATG11, which is required for selective targeting of cellular components to the vacuole for degradation, did not reduce CLS. The nonessential amino acids isoleucine and valine, and the essential amino acid leucine, extended CLS in autopha...

Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation

Aging Cell — Wed, 29 Apr 2009 04:00:00 +0100

Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18[ndash]91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive ...

Diminished contraction-induced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle

Aging Cell — Tue, 21 Apr 2009 23:00:00 +0100

The intent of this study was to determine whether aging affects signaling pathways involved in mitochondrial biogenesis in response to a single bout of contractile activity. Acute stimulation (1 Hz, 5 min) of the tibialis anterior (TA) resulted in a greater rate of fatigue in old (36 month), compared to young (6 month) F344XBN rats, which was associated with reduced ATP synthesis and a lower mitochondrial volume. To investigate fiber type-specific signaling, the TA was sectioned into red (RTA) and white (WTA) portions, possessing two- to 2.5-fold differences in mitochondrial content. The expression and contraction-mediated phosphorylation of p38, MKK3/6, CaMKII and AMPK[alpha] were assessed. Kinase protein expression tended to be higher in fiber sections with lower mitochondrial content, s...

Do mtDNA deletions drive premature aging in mtDNA mutator mice?

Aging Cell — Tue, 21 Apr 2009 23:00:00 +0100

Deletions in mitochondrial DNA (mtDNA) have long been suspected to be involved in mammalian aging, but their role remains controversial. Recent research has demonstrated that relatively higher levels of mtDNA deletions correlate with premature aging in mtDNA mutator mice, which led to the conclusion that premature aging in these mice is driven by mtDNA deletions. However, it is reported here that the absolute level of deletions in mutator mice is quite low, especially when compared with the level of point mutations in these mice. It is thus argued that the available data are insufficient to conclude that mtDNA mutations drive premature aging in mtDNA mutator mice. It remains possible that clonal expansion of mtDNA deletions may result in sufficiently high levels to play a role in age-relat...

IGF-1, nutrition and aging: the big picture

Aging Cell — Fri, 06 Mar 2009 05:00:00 +0100

(Source: Aging Cell)

Aging, IGF-1, and diet

Aging Cell — Thu, 05 Mar 2009 05:00:00 +0100

(Source: Aging Cell)

ING1a expression increases during replicative senescence and induces a senescent phenotype

Aging Cell — Tue, 07 Oct 2008 04:00:00 +0100

The ING family of tumor suppressor proteins affects cell growth, apoptosis and response to DNA damage by modulating chromatin structure through association with different HAT and HDAC complexes. The major splicing isoforms of the ING1 locus are ING1a and INGlb. While INGlb plays a role in inducing apoptosis, the function of ING1a is currently unknown. Here we show that alternative splicing of the ING1 message alters the INGla:INGlb ratio by ~30-fold in senescent compared to low passage primary fibroblasts. INGla antagonizes INGlb function in apoptosis, induces the formation of structures resembling senescence-associated heterochromatic foci containing heterochromatin protein 1 gamma, the accumulation of senescence-associated [beta]-galactosidase activity and promotes senescent cell morphol...

Mitochondrial turnover in liver is fast in vivo and is accelerated by dietary restriction: application of a simple dynamic model

Aging Cell — Sat, 06 Sep 2008 04:00:00 +0100

'Mitochondrial dysfunction', which may result from an accumulation of damaged mitochondria in cells due to a slowed-down rate of mitochondrial turnover and inadequate removal of damaged mitochondria during aging, has been implicated as both cause and consequence of the aging process and a number of age-related pathologies. Despite growing interest in mitochondrial function during aging, published data on mitochondrial turnover are scarce, and differ from each other by up to one order of magnitude. Here we demonstrate that re-utilization of the radioactively labelled precursor in pulse-chase assays is the most likely cause of significant overestimation of mitochondrial turnover rates. We performed a classic radioactive label pulse-chase experiment using 14C NaHCO3, whose 14C is incorporated...

p16INK4a-induced senescence is disabled by melanoma-associated mutations

Aging Cell — Fri, 05 Sep 2008 04:00:00 +0100

The p16INK4a-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression. Senescence can be overcome if the pathway is not fully engaged, and this may occur when p16INK4a is inactivated. p16INK4a is frequently altered in human cancer and germline mutations affecting p16INK4a have been linked to melanoma susceptibility. To characterize the functions of melanoma-associated p16INK4a mutations, in terms of promoting proliferative arrest and initiating senescence, we utilized an inducible expression system in a melanoma cell model. We show that wild-type p16INK4a promotes rapid cell cycle arrest that leads to a senescence programme characterized by the appearance ...

Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans

Aging Cell — Fri, 05 Sep 2008 04:00:00 +0100

Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg[minus]1 of body weight per day to 0.95 g kg[minus]1 of body weight per day for 3 weeks in six...

Mitochondrial iron accumulation with age and functional consequences

Aging Cell — Fri, 05 Sep 2008 04:00:00 +0100

During the aging process, an accumulation of non-heme iron disrupts cellular homeostasis and contributes to the mitochondrial dysfunction typical of various neuromuscular degenerative diseases. Few studies have investigated the effects of iron accumulation on mitochondrial integrity and function in skeletal muscle and liver tissue. Thus, we isolated liver mitochondria (LM), as well as quadriceps-derived subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), from male Fischer 344× Brown Norway rats at 8, 18, 29 and 37 months of age. Non-heme iron content in SSM, IFM and LM was significantly higher with age, reaching a maximum at 37 months of age. The mitochondrial permeability transition pore (mPTP) was more susceptible to the opening in aged mitochondria containing high ...

Mutation in aging mice occurs in diverse cell types that proliferate postmutation

Aging Cell — Wed, 27 Aug 2008 04:00:00 +0100

To determine the relationship between aging, cell proliferation and mutation in different cell types, hearts, brains and kidneys from G11 PLAP mice between 1 week and 24 months of age were examined. Mutant cells were detected in tissue sections by staining for Placental Alkaline Phosphatase (PLAP) activity, an activity that marks cells that have sustained a frameshift mutation in a mononucleotide tract inserted into the coding region of the human gene encoding PLAP. The number of PLAP+ cells increased with age in all three tissues. The types of cells exhibiting a mutant phenotype included cells that are proliferative, such as kidney epithelial cells, and cells that do not frequently replicate, such as cardiac muscle cells and neurons. In the brain, PLAP+ cells appeared in various locations...

Some highlights of research on aging with invertebrates, 2008

Aging Cell — Sat, 09 Aug 2008 04:00:00 +0100

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for in-depth analysis. This year, the first quantitative estimate of evolutionary conservation of genetic effects on lifespan has pointed to the key importance of genes involved in protein synthesis, a finding confirmed and extended by experimental work. Work in Caenorhabditis elegans and Drosophila has highlighted the importance of phase 2 detoxification in extension of lifespan by reduced insulin/Igf-like signalling. Thorough characterization of systems for dietary restriction in C. elegans is starting to show differences in the mechanisms by which these interventions extend lifespan and has revealed a requirement for autophagy. The response to heat shock ...

Aging Cell manuscripts on the road to PubMed Central: shifting from manual to automatic transmission

Aging Cell — Tue, 15 Jul 2008 07:17:13 +0100

(Source: Aging Cell)

Corrigendum

Aging Cell — Sun, 13 Jul 2008 04:00:00 +0100

(Source: Aging Cell)

Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster

Aging Cell — Wed, 18 Jun 2008 18:01:44 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The inability to properly balance energy intake and expenditure with nutrient supply forms the basis for some of today's most pressing health issues, including diabetes and obesity. Mechanisms of nutrient homeostasis may also lie at the root of ... (Source: Aging Cell)

Aging-related changes in astrocytes in the rat retina: imbalance between cell proliferation and cell death reduces astrocyte availability

Aging Cell — Wed, 18 Jun 2008 00:05:18 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats ... (Source: Aging Cell)

Aging-related differences in basal heat shock protein 70 levels in lymphocytes are linked to altered frequencies of lymphocyte subsets

Aging Cell — Wed, 18 Jun 2008 00:05:03 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Cell stress responses are ubiquitous in all organisms and are characterized by the induced synthesis of heat shock proteins (Hsp). Previous studies as well as recent reports by our group have consistently suggested that aging leads to an increase ... (Source: Aging Cell)

Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation

Aging Cell — Wed, 18 Jun 2008 00:04:38 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Although chronological donor age is the most potent predictor of long-term outcome after renal transplantation, it does not incorporate individual differences of the aging-process itself. We therefore hypothesized that an estimate of biological ... (Source: Aging Cell)

Stem Cell Review Series: Aging of the skeletal muscle stem cell niche

Aging Cell — Wed, 18 Jun 2008 00:04:23 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Declining stem cell function during aging contributes to impaired tissue function. Muscle-specific stem cells (‘satellite cells’) are responsible for generating new muscle in response to injury in the adult. However, aged muscle displays a ... (Source: Aging Cell)

Stem Cell Review Series: Regulating highly potent stem cells in aging: environmental influences on plasticity

Aging Cell — Wed, 18 Jun 2008 00:04:00 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Significant advances in the past decade have revealed that a large number of highly plastic stem cells are maintained in humans through adulthood and are present even in older adults. These findings are notable in light of the reduced capacity ... (Source: Aging Cell)

Telomeres and race: what can we learn about human biology from health differentials?

Aging Cell — Tue, 27 May 2008 22:32:27 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The advent of molecular technology that can be applied across large population samples has added – rather than reduced – complexity in the analysis of the intertwined effects of social history and heritable factors on health outcomes. The report ... (Source: Aging Cell)

Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study

Aging Cell — Tue, 27 May 2008 19:53:37 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Leukocyte telomere length (LTL) is ostensibly a bio-indicator of human aging. Here we report that African Americans have longer LTL than whites. We studied cross-sectionally 2453 individuals from the National Heart, Lung, and Blood Institute (... (Source: Aging Cell)

Aging Cell manuscripts on the road to PubMed Central: shifting from manual to automatic transmission

Aging Cell — Thu, 22 May 2008 18:01:53 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. (Source: Aging Cell)

Erratum: Corrigendum

Aging Cell — Mon, 12 May 2008 08:19:03 +0100

Aging Cell, Volume 7, Issue 3, Page 445, June 2008. (Source: Aging Cell)

Effect of aging on neurogenesis in the canine brain

Aging Cell — Mon, 12 May 2008 08:18:22 +0100

Aging Cell, Volume 7, Issue 3, Page 368-374, June 2008. Summary An age-dependent decline in hippocampal neurogenesis has been reported in laboratory rodents. Environmental enrichment proved to be a strong trigger of neurogenesis in young and aged laboratory rodents, which are generally kept in facilities with ... (Source: Aging Cell)

Age structure changes and extraordinary lifespan in wild medfly populations

Aging Cell — Mon, 12 May 2008 08:14:38 +0100

Aging Cell, Volume 7, Issue 3, Page 426-437, June 2008. Summary The main purpose of this study was to test the hypotheses that major changes in age structure occur in wild populations of the Mediterranean fruit fly (medfly) and that a substantial fraction of individuals survive to middle age and beyond (> 3–4 ... (Source: Aging Cell)

Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress

Aging Cell — Fri, 09 May 2008 18:02:48 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Many nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to ... (Source: Aging Cell)

Age-related increase of superoxide generation in the brains of mammals and birds

Aging Cell — Fri, 09 May 2008 11:49:23 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Oxidative stress, an imbalance between endogenous levels of oxygen radicals and antioxidative defense, increases with aging. However, it is not clear which of these two factors is the more critical. To clarify the production of oxygen radicals ... (Source: Aging Cell)

Visceral adipose tissue modulates mammalian longevity

Aging Cell — Fri, 25 Apr 2008 18:02:27 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Caloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a ... (Source: Aging Cell)

Perturbation of wild-type lamin A metabolism results in a progeroid phenotype

Aging Cell — Wed, 23 Apr 2008 18:01:44 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Mutations in the lamin A/C gene cause the rare genetic disorder Hutchinson–Gilford progeria syndrome (HGPS). The prevalent mutation results in the production of a mutant lamin A protein with an internal 50 amino acid deletion which causes a ... (Source: Aging Cell)

Longevity–fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients

Aging Cell — Tue, 22 Apr 2008 18:54:11 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Although it is widely known that dietary restriction (DR) not only extends the longevity of a wide range of species but also reduces their reproductive output, the interrelationship of DR, longevity extension and reproduction is not well ... (Source: Aging Cell)

Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity

Aging Cell — Tue, 22 Apr 2008 18:53:50 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The premature human aging Werner syndrome (WS) is caused by mutation of the RecQ-family WRN helicase, which is unique in possessing also 3'–5' exonuclease activity. WS patients show significant genomic instability with elevated cancer incidence. ... (Source: Aging Cell)

Oxidation as a crucial reaction for cholesterol to induce tissue degeneration: CD36 overexpression in human promonocytic cells treated with a biologically relevant oxysterol mixture

Aging Cell — Tue, 08 Apr 2008 18:02:35 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Oxidative stress, inflammation and altered cholesterol metabolism and levels are among the pathogenetic mechanisms of cognitive impairment that may accompany aging. Within the research area of hypercholesterolemia and age-related disease ... (Source: Aging Cell)

Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth

Aging Cell — Tue, 08 Apr 2008 12:23:24 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary In recent years, the intracellular reactive oxygen species (ROS) levels have gained increasing attention as a critical regulator of cellular proliferation. We investigated the hypothesis that manganese superoxide dismutase (MnSOD) activity ... (Source: Aging Cell)

Increased mechanosensitivity and nuclear stiffness in Hutchinson–Gilford progeria cells: effects of farnesyltransferase inhibitors

Aging Cell — Tue, 08 Apr 2008 12:23:06 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Hutchinson–Gilford progeria syndrome (HGPS), reportedly a model for normal aging, is a genetic disorder in children marked by dramatic signs suggestive for premature aging. It is usually caused by de novo mutations in the nuclear envelope protein ... (Source: Aging Cell)

Aging and cancer cell biology, 2008

Aging Cell — Tue, 08 Apr 2008 12:22:50 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary There is increasing support for the idea that aging and cancer are intimately connected by the activity of specific genes and the cellular responses to potentially oncogenic insults. This Hot Topics review discusses some recently published ... (Source: Aging Cell)

Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans

Aging Cell — Tue, 08 Apr 2008 12:22:28 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Dietary restriction increases lifespan and slows the onset of age-associated disease in organisms from yeast to mammals. In humans, several age-related diseases are associated with aberrant protein folding or aggregation, including ... (Source: Aging Cell)

Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings

Aging Cell — Tue, 08 Apr 2008 12:21:53 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Growth hormone deficiency or resistance resulting from spontaneous or experimentally produced mutations in laboratory mice delay aging and increase lifespan. Alterations in insulin-like growth factor-1 (IGF-1) and insulin signaling emerged as ... (Source: Aging Cell)

Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q

Aging Cell — Thu, 27 Mar 2008 18:06:45 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Coenzyme Qn is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Caenorhabditis elegans fed Escherichia coli devoid of Q8 have a significant lifespan extension when compared to C. elegans ... (Source: Aging Cell)

Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor

Aging Cell — Tue, 25 Mar 2008 18:01:42 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Age-associated changes in stem cell populations have been implicated in age-related diseases, including cancer. However, little is known about the underlying molecular mechanisms that link aging to the modulation of adult stem cell populations. ... (Source: Aging Cell)

Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila

Aging Cell — Tue, 25 Mar 2008 14:18:45 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Adult stem cells are important in replenishing aged cells to maintain tissue homeostasis. Aging in turn may exert profound effects on stem cell's regenerative potential, but to date the mechanisms of such stem cell aging are poorly understood, ... (Source: Aging Cell)

Erratum: Corrigendum

Aging Cell — Thu, 13 Mar 2008 18:02:16 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. (Source: Aging Cell)

Valproic acid extends Caenorhabditis elegans lifespan

Aging Cell — Sat, 08 Mar 2008 19:00:57 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Aging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging. Caenorhabditis elegans is a valuable model for studies of animal aging, and the ... (Source: Aging Cell)

Role of neurogenesis in age-related memory disorders

Aging Cell — Fri, 07 Mar 2008 19:01:37 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Neuroplasticity is characterized by growth and branching of dendrites, remodeling of synaptic contacts, and neurogenesis, thus allowing the brain to adapt to changes over time. It is maintained in adulthood but strongly repressed during aging. An ... (Source: Aging Cell)

Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts

Aging Cell — Fri, 07 Mar 2008 15:22:53 +0100

In this study, we tested ... (Source: Aging Cell)

Age-related reduction in retinal deimination levels in the F344BN rat

Aging Cell — Tue, 04 Mar 2008 19:01:42 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Increased deimination and peptidyl arginine deiminase type 2 (PAD2) expression has been observed in age-related neurodegenerative diseases without discrimination between their aging and disease component. Here, we describe reduced levels of ... (Source: Aging Cell)

Hot topics: advances in vertebrate aging research 2007

Aging Cell — Thu, 21 Feb 2008 19:02:43 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Among this year's highlights in vertebrate aging research, we find a study in which, contrary to the oxidative stress hypothesis of aging, reduced expression of a major cellular antioxidant, glutathione peroxidase 4, led to a small increase in ... (Source: Aging Cell)

Epidermal stem cells are retained in vivo throughout skin aging

Aging Cell — Thu, 21 Feb 2008 11:16:48 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation. It is currently unknown whether epidermal stem cells influence or are affected by ... (Source: Aging Cell)

Functional analysis of the Drosophila immune response during aging

Aging Cell — Thu, 21 Feb 2008 11:16:27 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary One of the most dramatic changes associated with aging involves immunity. In aging mammals, immune function declines and chronic inflammation develops. The biological significance of this phenomenon and its relationship with aging is a priority ... (Source: Aging Cell)

Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

Aging Cell — Thu, 21 Feb 2008 10:39:24 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Studies of mutations affecting lifespan in Caenorhabditis elegans show that mitochondrial generation of reactive oxygen species (ROS) plays a major causative role in organismal aging. Here, we describe a novel mechanism for regulating ... (Source: Aging Cell)

Drosophila lifespan control by dietary restriction independent of insulin-like signaling

Aging Cell — Wed, 20 Feb 2008 19:00:48 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Reduced insulin/insulin-like growth factor (IGF) signaling may be a natural way for the reduction of dietary nutrients to extend lifespan. While evidence challenging this hypothesis is accumulating with Caenorhabditis elegans, for Drosophila ... (Source: Aging Cell)

Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype

Aging Cell — Wed, 20 Feb 2008 10:52:30 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary A number of studies have been conducted recently on the model organism Drosophila to determine the function of genes involved in human disease, including those implicated in neurological disorders, cancer and metabolic and cardiovascular ... (Source: Aging Cell)

Genes encoding longevity: from model organisms to humans

Aging Cell — Tue, 05 Feb 2008 19:02:51 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance and repair mechanisms ... (Source: Aging Cell)

Acquired temperature-sensitive paralysis as a biomarker of declining neuronal function in aging Drosophila

Aging Cell — Tue, 05 Feb 2008 11:24:54 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary General locomotor activity decreases with normal aging in animals and could be partially explained by decreases in neuronal function. Voltage-gated Na+ channels are essential in initiating and propagating rapid electrical impulses underlying ... (Source: Aging Cell)

Role of dFOXO in lifespan extension by dietary restriction in Drosophila melanogaster: not required, but its activity modulates the response

Aging Cell — Wed, 30 Jan 2008 17:16:23 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Dietary restriction (DR) increases lifespan in diverse organisms. However, the mechanisms by which DR increases survival are unclear. The insulin/IGF-like signaling (IIS) pathway has been implicated in the response to DR in some studies, while in ... (Source: Aging Cell)

Architectural changes in the thymus of aging mice

Aging Cell — Wed, 30 Jan 2008 14:27:45 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Age-associated thymic involution is one of the most dramatic and ubiquitous changes in the immune system, although the precise mechanisms involved still remain obscured. Several hypotheses have been proposed incorporating extrinsic and intrinsic ... (Source: Aging Cell)

Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling

Aging Cell — Wed, 30 Jan 2008 14:26:56 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Beta-site APP-cleaving enzyme 1 (BACE1) expression is elevated in the brains of Alzheimer's disease (AD) patients and in aged-animal models. Because both AD and aging are associated with disrupted calcium homeostasis, we investigated the role of ... (Source: Aging Cell)

Elevated Ras/protein kinase A activity in Saccharomyces cerevisiae reduces proliferation rate and lifespan by two different reactive oxygen species-dependent routes

Aging Cell — Wed, 30 Jan 2008 14:26:35 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Cells with overactive RAS/protein kinase A (PKA) signaling, such as RAS2Val19 cells, exhibit reduced proliferation rates and accelerated replicative senescence. We show here that the extended generation time of RAS2Val19 cells is the result of ... (Source: Aging Cell)

Evidence that age-related changes in p38 MAP kinase contribute to the decreased steroid production by the adrenocortical cells from old rats

Aging Cell — Wed, 30 Jan 2008 14:26:26 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The current studies were initiated to investigate whether excessive oxidative stress exerts its antisteroidogenic action through modulation of oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathways. Western blot analysis ... (Source: Aging Cell)

Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age

Aging Cell — Wed, 30 Jan 2008 14:25:06 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary A remarkable up-regulation of neurogenesis through increased proliferation of neural stem/progenitor cells (NSCs) is a well-known plasticity displayed by the young dentate gyrus (DG) following brain injury. To ascertain whether this plasticity is ... (Source: Aging Cell)

Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice

Aging Cell — Wed, 16 Jan 2008 17:22:27 +0100

Aging Cell, Volume 7, Issue 1, Page 78-88, February 2008. Summary The Sir2 (silent information regulator 2) family of NAD-dependent deacetylases regulates aging and longevity across a wide variety of organisms, including yeast, worms, and flies. In mammals, the Sir2 ortholog Sirt1 promotes fat mobilization, ... (Source: Aging Cell)

Dynamic regulation of PGC-1α localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response

Aging Cell — Wed, 16 Jan 2008 17:21:59 +0100

We report that mitochondria are regulated in response to oxidative stress and calorie restriction through a shared mechanism involving ... (Source: Aging Cell)

Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38

Aging Cell — Wed, 16 Jan 2008 17:21:53 +0100

Aging Cell, Volume 7, Issue 1, Page 112-118, February 2008. Summary Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-β estradiol (0.2 nm) or with ... (Source: Aging Cell)

Aging Cell – the Cowen era: looking back downstream from calmer waters

Aging Cell — Thu, 03 Jan 2008 19:06:43 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. (Source: Aging Cell)

Amyloid β-peptide 31–35-induced neuronal apoptosis is mediated by caspase-dependent pathways via cAMP-dependent protein kinase A activation

Aging Cell — Wed, 19 Dec 2007 19:01:29 +0100

This study aims to investigate the roles of the protein kinase A (PKA)- and caspase-dependent pathways in amyloid β-peptide 31–35 (Aβ[31–35])-induced apoptosis, and the mechanisms of neuroprotection by group III metabotropic glutamate receptor (... (Source: Aging Cell)

Delayed kinetics of DNA double-strand break processing in normal and pathological aging

Aging Cell — Wed, 19 Dec 2007 11:17:00 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Accumulation of DNA damage may play an essential role in both cellular senescence and organismal aging. The ability of cells to sense and repair DNA damage declines with age. However, the underlying molecular mechanism for this age-dependent ... (Source: Aging Cell)

Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a

Aging Cell — Wed, 19 Dec 2007 11:16:53 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary In vertebrates and invertebrates, relationships between diet and health are controlled by a conserved signalling pathway responsive to insulin-like ligands. In invertebrate models for example, forkhead transcription factor family O (FOXO) ... (Source: Aging Cell)

Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage

Aging Cell — Wed, 19 Dec 2007 11:16:44 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Cellular senescence is an important phenomenon in decreased cellular function. Recently, it was shown that cellular senescence is induced in proliferating cells within a short period of time by oxidative stresses. This phenomenon is known as ... (Source: Aging Cell)

Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice

Aging Cell — Mon, 26 Nov 2007 19:02:59 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Fundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal ... (Source: Aging Cell)

Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis

Aging Cell — Tue, 20 Nov 2007 11:40:21 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Osteoporosis and the associated risk of fracture are major clinical challenges in the elderly. Telomeres shorten with age in most human tissues, including bone, and because telomere shortening is a cause of cellular replicative senescence or ... (Source: Aging Cell)

Mitochondrially encoded cysteine predicts animal lifespan

Aging Cell — Tue, 20 Nov 2007 11:40:21 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary The role of genetic factors in the determination of lifespan is undisputed. However, numerous successful efforts to identify individual genetic modulators of longevity have not yielded yet a quantitative measure to estimate the lifespan of a ... (Source: Aging Cell)

Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice

Aging Cell — Wed, 14 Nov 2007 01:34:41 +0100

Aging Cell, Volume 6, Issue 6, Page 827-839, December 2007. Summary Caloric restriction, leanness and decreased activity of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling are associated with increased longevity in a wide range of organisms from Caenorhabditis elegans to humans. Fat-specific ... (Source: Aging Cell)

Aging Cell — Wed, 14 Nov 2007 01:34:40 +0100

Aging Cell, Volume 6, Issue 6, Page i-vi, December 2007. (Source: Aging Cell)

Presbyopia and heat: changes associated with aging of the human lens suggest a functional role for the small heat shock protein, α-crystallin, in maintaining lens flexibility

Aging Cell — Wed, 31 Oct 2007 18:08:25 +0100

We present evidence that presbyopia may be the ... (Source: Aging Cell)

Chronic calorie restriction increases susceptibility of laboratory mice (Mus musculus) to a primary intestinal parasite infection

Aging Cell — Wed, 31 Oct 2007 09:03:33 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary Long-term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice (Mus musculus), it was hypothesized that mice ... (Source: Aging Cell)

Influence of cardiac-specific overexpression of insulin-like growth factor 1 on lifespan and aging-associated changes in cardiac intracellular Ca2+ homeostasis, protein damage and apoptotic protein expression

Aging Cell — Wed, 31 Oct 2007 09:03:33 +0100

Aging Cell, Volume 0, Issue 0, Page ???, December 2004. Summary A fall in circulating levels of cardiac survival factor insulin-like growth factor 1 (IGF-1) contributes to cardiac aging. To better understand the role of IGF-1 in cardiac aging, we examined the influence of cardiac IGF-1 overexpression on ... (Source: Aging Cell)

Remarkable Longevity and Stress Resistance of Nematode PI3K-Null Mutants

Aging Cell — Thu, 11 Oct 2007 20:39:46 +0100

Aging Cell Volume 0, Issue ja. Summary The great majority of life-span augmenting mutations were discovered in the nematode Caenorhabditis elegans. In particular, genetic disruption of insulinlike signaling extends longevity 1.5- to 3-fold in the nematode, and to lesser degrees in othe... (Source: Aging Cell)

Mitochondrial function and apoptotic susceptibility in aging skeletal muscle

Aging Cell — Thu, 11 Oct 2007 20:39:46 +0100

Aging Cell Volume 0, Issue ja. Summary During aging, skeletal muscle undergoes sarcopenia which is characterized by a loss of muscle cell mass and alterations in contractile function. The origin of these decrements is unknown, but evidence suggests that they can be partly attributed to... (Source: Aging Cell)

Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity

Aging Cell — Tue, 09 Oct 2007 20:39:51 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Vascular aging is characterized by increased oxidative stress, impaired nitric oxide (NO) bioavailability and enhanced apoptotic cell death. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower ... (Source: Aging Cell)

Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan

Aging Cell — Tue, 09 Oct 2007 18:01:13 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Mesenchymal stem cells (MSC) are capable of differentiating into bone, fat, cartilage, tendon and other organ progenitor cells. Despite the abundance of MSC within the organism, little is known about their in vivo properties or about their corresp... (Source: Aging Cell)

Chronic Calorie Restriction Increases Susceptibility of Laboratory Mice (Mus musculus) to a Primary Intestinal Parasite Infection

Aging Cell — Tue, 25 Sep 2007 00:17:38 +0100

Aging Cell Volume 0, Issue ja. Summary Long-term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice (Mus musculus), it was hypothesized that mice gi... (Source: Aging Cell)

Presbyopia and heat. Changes associated with aging of the human lens, suggest a functional role for the small heat shock protein, α-crystallin, in maintaining lens flexibility.

Aging Cell — Tue, 25 Sep 2007 00:17:38 +0100

We present evidence that presbyopia may be the result... (Source: Aging Cell)

Mitochondrial Gene Expression and Increased Oxidative Metabolism: Role in Increased Lifespan of Fat-Specific Insulin Receptor Knockout Mice

Aging Cell — Tue, 25 Sep 2007 00:17:37 +0100

Aging Cell Volume 0, Issue ja. SUMMARY Caloric restriction, leanness and decreased activity of insulin/IGF-1 receptor signaling are associated with increased longevity in a wide range of organisms from C. elegans to humans. Mice with a fat-specific knockout of the insulin receptor (FIR... (Source: Aging Cell)

Is Sirt1 a miracle bullet for longevity?

Aging Cell — Tue, 25 Sep 2007 00:17:37 +0100

Aging Cell Volume 0, Issue ja. Summary The Sir2 (silent information regulator 2) family of NAD-dependent deacetylases has been implicated in the regulation of aging and longevity across a wide variety of organisms. Although controversial, Sir2 proteins have also been implicated as key ... (Source: Aging Cell)

Influence of Cardiac Specific Overexpression of Insulin-Like Growth Factor-1 on Lifespan and Aging-Associated Changes in Cardiac Intracellular Ca2+ Homeostasis, Protein Damage and Apoptotic Protein Expression

Aging Cell — Tue, 25 Sep 2007 00:17:37 +0100

Aging Cell Volume 0, Issue ja. SUMMARY A fall in circulating levels of cardiac survival factor insulin-like growth factor-1 (IGF-1) contributes to cardiac aging. To better understand the role of IGF-1 in cardiac aging, we examined the influence of cardiac IGF-1 overexpression on lifesp... (Source: Aging Cell)

The NIA Interventions Testing Program Announces the 2008 Solicitation of Proposals

Aging Cell — Mon, 17 Sep 2007 18:00:34 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. (Source: Aging Cell)

Vascular O2.− and H2O2 production and oxidative stress resistance in two closely related rodent species with disparate longevity

Aging Cell — Fri, 14 Sep 2007 22:39:22 +0100

Aging Cell Volume 0, Issue ja. Summary Vascular aging is characterized by increased oxidative stress, impaired NO bioavailability and enhanced apoptotic cell death. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower production of r... (Source: Aging Cell)

Protein Translation, 2007

Aging Cell — Fri, 14 Sep 2007 22:39:20 +0100

Aging Cell Volume 0, Issue ja. Summary Translation of RNA to protein is essential for life. It should perhaps not be surprising, therefore, that appropriate regulation of translation plays a key role in determining longevity. This Hot Topic Review discusses papers published in the last... (Source: Aging Cell)

Telomere length predicts survival independent of genetic influences

Aging Cell — Fri, 14 Sep 2007 22:39:20 +0100

Aging Cell Volume 0, Issue ja. Summary Telomeres prevent the loss of coding genetic material during chromosomal replication. Prior research suggests that shorter telomere length may be associated with lower survival. Because genetic factors are important for individual differences in b... (Source: Aging Cell)

Transcriptional Instability is Not a Universal Attribute of Aging

Aging Cell — Fri, 07 Sep 2007 14:32:56 +0100

Aging Cell Volume 0, Issue ja. Summary It has been proposed that cumulating somatic mutations contribute to the aging process by disrupting the transcriptional networks which regulate cell structure and function. Experimental support for this model emerged from a recent study of cardio... (Source: Aging Cell)

What is OnlineAccepted?

Aging Cell — Tue, 04 Sep 2007 06:46:30 +0100

Aging Cell Volume 0, Issue ja. What is OnlineAccepted? OnlineAccepted is a Blackwell Synergy service whereby peer reviewed, accepted articles or abstracts are published online as and when they are ready, prior to their ultimate inclusion in a print or online issue and without having be... (Source: Aging Cell)

Some highlights of research on aging with invertebrates, 2006–2007

Aging Cell — Fri, 24 Aug 2007 14:18:11 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary The invertebrate model organisms continue to be engines of discovery in aging research. Recent work with Drosophila stem cells has thrown light on their human equivalents, and on the role of stem cells and their niches in the decline in fecundity ... (Source: Aging Cell)

Sexual selection affects lifespan and aging in the seed beetle

Aging Cell — Fri, 24 Aug 2007 14:18:11 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Sexual selection in general, and sexual conflict in particular, should affect the evolution of lifespan and aging. Using experimental evolution, we tested whether removal of sexual selection leads to the evolution of accelerated or decelerated sen... (Source: Aging Cell)

Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins

Aging Cell — Wed, 15 Aug 2007 18:00:27 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Calorie restriction (CR) extends the mean and maximum lifespan of a wide variety of organisms ranging from yeast to mammals, although the molecular mechanisms of action remain unclear. For the budding yeast Saccharomyces cerevisiae reducing glucos... (Source: Aging Cell)

Caenorhabditis elegans integrates food and reproductive signals in lifespan determination

Aging Cell — Wed, 15 Aug 2007 10:25:18 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Dietary restriction extends lifespan and inhibits reproduction in many species. In Caenorhabditis elegans, inhibiting reproduction by germline removal extends lifespan. Therefore, we asked whether the effect of dietary restriction on lifespan migh... (Source: Aging Cell)

Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their life span

Aging Cell — Mon, 13 Aug 2007 08:57:02 +0100

Aging Cell Volume 0, Issue ja. Abstract Mesenchymal stem cells (MSC) are capable of differentiating into bone, fat, cartilage, tendon, and other organ progenitor cells. Despite the abundance of MSC within the organism, little is known about their in vivo properties or about their corre... (Source: Aging Cell)

SIRT1 transgenic mice show phenotypes resembling calorie restriction

Aging Cell — Mon, 13 Aug 2007 08:57:01 +0100

Aging Cell Volume 0, Issue ja. Summary We generated mice that overexpress the sirtuin, SIRT1. Transgenic mice have been generated by knocking in SIRT1 cDNA into the β-actin locus. Mice that are hemizygous for this transgene express normal levels of β-actin and higher levels of SIRT1 pr... (Source: Aging Cell)

Loss of pregnancy-associated plasma protein A extends lifespan in mice

Aging Cell — Mon, 06 Aug 2007 20:57:16 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30–40% both mean and maximum lifespan with no reduction in food intake or seco... (Source: Aging Cell)

Mitochondrial DNA deletions induce the adenosine monophosphate-activated protein kinase energy stress pathway and result in decreased secretion of some proteins

Aging Cell — Thu, 26 Jul 2007 18:00:27 +0100

Aging Cell Volume 0, Issue 0, Page ???-???. Summary Mitochondrial DNA (mtDNA) deletions occur sporadically in zygotic and somatic tissues and reach their highest concentration in substantia nigra. Previously, we noted the increase of the adenosine monophosphate (AMP)-activated protein kinase (AMPK)... (Source: Aging Cell)

Sexual selection affects lifespan and aging in a beetle

Aging Cell — Sat, 21 Jul 2007 12:41:09 +0100

Aging Cell Volume 0, Issue ja. SUMMARY Sexual selection in general, and sexual conflict in particular, should affect the evolution of lifespan and aging. Using experimental evolution, we tested whether removal of sexual selection leads to the evolution of rapid senescence. We subjected... (Source: Aging Cell)

Some highlights of research on aging with invertebrates, 2006-2007

Aging Cell — Sat, 21 Jul 2007 12:41:08 +0100

Aging Cell Volume 0, Issue ja. Summary The invertebrate model organisms continue to be engines of discovery in aging research. Recent work with Drosophila stem cells has thrown light on their human equivalents, and on the role of stem cells and their niches in the decline in fecundity ... (Source: Aging Cell)