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A Call for Matching Donors for the LEV Foundation " Robust Mouse Rejuvenation 2 " Fundraiser
The Longevity Escape Velocity (LEV) Foundation was founded by Aubrey de Grey to address an important missing aspect of the ongoing work to produce treatments that target the underlying mechanisms of aging. While the research and development community has made sizable strides in the past decade, and the first rejuvenation therapies now exist in at least prototype form, it remains the case that next to no-one is conducting combination studies that use two or more of these interventions. When considering therapies that can repair forms of the cell and tissue damage that cause aging, it seems plausible that two different thera...
Source: Fight Aging! - September 22, 2023 Category: Research Authors: Reason Tags: Activism, Advocacy and Education Source Type: blogs
High-Throughput Screening of the Saccharomyces cerevisiae Genome for 2-Amino-3-Methylimidazo 4,5-f Quinoline Resistance Identifies Colon Cancer-Associated Genes
G3 (Bethesda). 2023 Sep 22:jkad219. doi: 10.1093/g3journal/jkad219. Online ahead of print.ABSTRACTHeterocyclic aromatic amines (HAAs) are potent carcinogenic agents found in charred meats and cigarette smoke. However, few eukaryotic resistance genes have been identified. We used Saccharomyces cerevisiae (budding yeast) to identify genes that confer resistance to 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). CYP1A2 and NAT2 activate IQ to become a mutagenic nitrenium compound. Deletion libraries expressing human CYP1A2 and NAT2 or no human genes were exposed to either 400 or 800 µM IQ for five or ten generations. DNA barc...
Source: Cancer Control - September 22, 2023 Category: Cancer & Oncology Authors: Michael Dolan Nick St John Faizan Zaidi Francis Doyle Michael Fasullo Source Type: research
PARylated PDHE1 α generates acetyl-CoA for local chromatin acetylation and DNA damage repair
Nat Struct Mol Biol. 2023 Sep 21. doi: 10.1038/s41594-023-01107-3. Online ahead of print.ABSTRACTChromatin relaxation is a prerequisite for the DNA repair machinery to access double-strand breaks (DSBs). Local histones around the DSBs then undergo prompt changes in acetylation status, but how the large demands of acetyl-CoA are met is unclear. Here, we report that pyruvate dehydrogenase 1α (PDHE1α) catalyzes pyruvate metabolism to rapidly provide acetyl-CoA in response to DNA damage. We show that PDHE1α is quickly recruited to chromatin in a polyADP-ribosylation-dependent manner, which drives acetyl-CoA generation to su...
Source: Mol Biol Cell - September 22, 2023 Category: Molecular Biology Authors: Jun Zhang Feng Chen Yuan Tian Wenchao Xu Qian Zhu Zhenhai Li Lingyu Qiu Xiaopeng Lu Bin Peng Xiangyu Liu Haiyun Gan Baohua Liu Xingzhi Xu Wei-Guo Zhu Source Type: research
Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis
J Orthop Surg Res. 2023 Sep 22;18(1):713. doi: 10.1186/s13018-023-04119-3.ABSTRACTOsteoarthritis (OA) is defined as a degenerative joint disease that can affect all tissues of the joint, including the articular cartilage, subchondral bone, ligaments capsule, and synovial membrane. The conventional nonoperative treatments are ineffective for cartilage repair and induce only symptomatic relief. Platelet-rich plasma (PRP) is a platelet concentrate derived from autologous whole blood with a high concentration of platelets, which can exert anti-inflammatory and regenerative effects by releasing multiple growth factors and cytok...
Source: Cell Research - September 22, 2023 Category: Cytology Authors: Zhengchao Wang Pengfei Zhu Bokai Liao Hongbo You Yu Cai Source Type: research
Mesenchymal Stem Cells as an Adjuvant Tool to Induce Regeneration and Repair in Marginal Renal Allografts
AbstractPurpose of ReviewMesenchymal stem cells (MSC) have been largely studied for more than three decades and have been proposed to treat a myriad of clinical conditions in dozens of clinical trials.Recent FindingsThey have become popular in transplant medicine due to their immunomodulatory properties with promising results. In the past decade, however, they have also been tested in the setting of organ preservation in reason of their ability to induce regeneration and repair in damaged tissues.SummaryThis manuscript reviews the worldwide experience relative to the use of MSC and their by-products, as therapeutic tool to...
Source: Current Transplantation Reports - September 22, 2023 Category: Transplant Surgery Source Type: research
Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis
Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells...
Source: Journal of Nanobiotechnology - September 22, 2023 Category: Nanotechnology Authors: Shu Zhao, Guanghui Xiu, Jian Wang, Yi Wen, Jinyuan Lu, Baitong Wu, Guangming Wang, Danjing Yang, Bin Ling, Dajiang Du and Jun Xu Tags: Research Source Type: research
Genes, Vol. 14, Pages 1838: Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus
Irene Rosa-Pérez
Juan Carlos Acal
Joana Blasco
Marta Naranjo-Castresana
Beatriz Ruz-Caracuel
Victoria E. F. Montaño
Cristina Ortega Patrón
M. Esther Rubio-Martín
Laura García-Fernández
Emi Rikeros-Orozco
María de Los Ángeles Gómez-Cano
Luna Delgado-Mora
Susana Noval
Elena Vallespín
Keratoconus is a corneal dystrophy that is one of the main causes of corneal transplantation and for which there is currently no effective treatment for all patients. The presentation of this disease in pediatric age is associated with rapid progression, a worse prognosis and, in 15–20% of ...
Source: Genes - September 22, 2023 Category: Genetics & Stem Cells Authors: Carmen Gonz ález-Atienza Elo ísa Sánchez-Cazorla Natalia Villoldo-Fern ández Almudena del Hierro Ana Boto Marta Guerrero-Carretero Mar ía Nieves-Moreno Natalia Arruti Patricia Rodr íguez-Solana Roc ío Mena Carmen Rodr íguez-Jiménez Irene Rosa-P Tags: Article Source Type: research
Results from Human Clinical Trials Do Not Support Metformin as a Longevity Drug
The SENS Research Foundation staff have carried out the public service of extensively discussing and dismantling the evidence commonly cited in support of metformin as a way to modestly slow aging, showing that said evidence is problematic, to say the least. Metformin might make life modestly better for diabetics, but it doesn't slow aging. This view of the human data matches the poor quality of the animal model data, in which metformin makes a poor showing in comparison to the robust data for a modest slowing of aging that is produced by the use of, say, mTOR inhibitors, or the practice of calorie restriction.
Rega...
Source: Fight Aging! - September 21, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Many Researchers and Companies Will Aim to Produce Small Molecule Reprogramming Therapies
The typical path for any program in biomedical research and development is to first demonstrate interesting results in animal studies using forms of genetic engineering or gene therapy, and then find small molecules that adjust the same mechanism. Small molecules are never as good as genetic manipulations, the size of the effect is always smaller, usually much smaller, and there are inevitably side-effects. Small molecule development is much easier to conduct, however, more familiar to investors and regulators and program managers, a well-trodden path. Thus while the future of medicine is gene therapy, in search of large e...
Source: Fight Aging! - September 21, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Triphenyl phosphate-induced pericardial edema in zebrafish embryos is reversible following depuration in clean water
Aquat Toxicol. 2023 Sep 18;263:106699. doi: 10.1016/j.aquatox.2023.106699. Online ahead of print.ABSTRACTTriphenyl phosphate (TPHP) - a widely used organophosphate-based flame retardant - blocks cardiac looping during zebrafish development in a concentration-dependent manner, a phenotype that is dependent on disruption of embryonic osmoregulation and pericardial edema formation. However, it's currently unclear whether (1) TPHP-induced effects on osmoregulation are driven by direct TPHP-induced injury to the embryonic epidermis and (2) whether TPHP-induced pericardial edema is reversible or irreversible following cessation ...
Source: Aquatic Toxicology - September 21, 2023 Category: Toxicology Authors: Jenna Wiegand John Hoang Sarah Avila-Barnard Charvita Nemarugommula Megan Ha Sharon Zhang Heather M Stapleton David C Volz Source Type: research
Urgent Juxtarenal Aortic Aneurysm Repair With Modified Off-the-shelf Endograft to Preserve Intercostal Arteries and Branch Incorporation by Transfemoral Access
CONCLUSION: t-Branch-modified endograft to limit aortic coverage is an alternative option in urgent cases to diminish the risk of spinal cord injury, and association of steerable sheaths with branch incorporation is leading complex aortic repairs to an even less invasive procedure.CLINICAL IMPACT: This paper highlights the possibility of performing complex endovascular aortic repair in an urgent setting with modification of an off-the-shelf multi branched endograft limiting intercostal arteries coverage, thereby diminishing the risk of spinal cord ischemia. This technical innovation provides an alternative for clinicians w...
Source: Pain Physician - September 21, 2023 Category: Anesthesiology Authors: Marcelo Ferreira Matheus Mannarino Rodrigo Cunha Diego Ferreira Luis Fernando Capotorto Source Type: research
Regulatory T cells require IL6 receptor alpha signaling to control skeletal muscle function and regeneration
Cell Metab. 2023 Sep 15:S1550-4131(23)00331-5. doi: 10.1016/j.cmet.2023.08.010. Online ahead of print.ABSTRACTMuscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function and regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs with increased expression of amphiregulin (Areg), EGFR, and ST2. Mechanistically, we find that mice lacking IL6Rα on T cells (TKO) harbor significant reductions in muscle Treg functionality and satelli...
Source: Cell Metabolism - September 21, 2023 Category: Cytology Authors: Maike Becker Sini S Joseph Francisco Garcia-Carrizo Robby Z Tom Daria Opaleva Isabelle Serr Matthias H Tsch öp Tim J Schulz Susanna M Hofmann Carolin Daniel Source Type: research
10-Patient Trial: Remarkable Responses in Pediatric Cancers
Clin Cancer Res. 2023 Sep 21. doi: 10.1158/1078-0432.CCR-23-2232. Online ahead of print.ABSTRACTA clinical trial of Nivolumab in 10 pediatric cancer patients with high tumor mutational burden demonstrated complete responses in 50% of patients. This result recapitulates multiple clinical trial results in high mutation burden adult cancers and may redefine best practice in the setting of germline DNA mismatch repair-based susceptibility.PMID:37733329 | DOI:10.1158/1078-0432.CCR-23-2232
Source: Clinical Cancer Research - September 21, 2023 Category: Cancer & Oncology Authors: Elaine R Mardis Source Type: research
Multi-scale cellular imaging of DNA double strand break repair
We describe different (live-cell) imaging modalities that can reveal details of the DNA double-strand break repair process across multiple time and spatial scales. In addition, recent developments are discussed in super-resolution imaging and single-molecule tracking, and how these technologies can be applied to elucidate details on structural compositions or dynamics of DNA double-strand break repair.PMID:37734176 | DOI:10.1016/j.dnarep.2023.103570
Source: DNA Repair - September 21, 2023 Category: Genetics & Stem Cells Authors: Tim Heemskerk Gerarda van de Kamp Jeroen Essers Roland Kanaar Maarten W Paul Source Type: research
Neuroprotective Potential of Punicalagin, a Natural Component of Pomegranate Polyphenols: A Review
J Integr Neurosci. 2023 Aug 9;22(5):113. doi: 10.31083/j.jin2205113.ABSTRACTNeurodegenerative diseases (NDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD), are major health problems worldwide. To date, available remedies against NDs are limited. In fact, current treatment options include drug intervention and nutritional therapy, which mainly focus on the repair of neuronal damage and functional monitoring. However, these treatments do not completely alleviate disease symptoms. Recently, eliminating harmful molecules, such as reactive oxygen species, and inhibiting neuroinflammation have become potential s...
Source: Journal of Integrative Neuroscience - September 21, 2023 Category: Neuroscience Authors: Peng Chen ZhiLei Guo Benhong Zhou Source Type: research
