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Therapy: Gene Therapy

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Cell Reprogramming via RNA Therapies
Gene therapies delivering mRNA produce a temporary production of proteins. An RNA molecule acts as a blueprint for a ribosome to assemble many copies of a specific protein, but this doesn't last long, and a few days of protein expression from a single treatment is a reasonable expectation in practice. This make RNA therapies suitable to produce partial reprogramming in an animal or patient. The Yamanaka factors are delivered for a long enough period of time to rejuvenate epigenetic patterns and restore mitochondrial function, but (hopefully) not long enough to convert any meaningful number of somatic cells into induced plu...
Source: Fight Aging! - March 15, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Further Exploration of In Vivo Reprogramming in Mice
Researchers are expanding their explorations of cellular reprogramming applied to living animals, delivering Yamanaka factors as a gene therapy. There are in principle ways to balance this sort of approach in order to minimize the conversion of somatic cells into induced pluripotent stem cells, and thus the risk of cancer, while maximizing the epigenetic rejuvenation and restoration of mitochondrial function that occurs as an early part of the reprogramming process. Forcing cells in aged tissues to act as though they are present in youthful tissues is expected to produce meaningful benefits to health, and indeed has...
Source: Fight Aging! - March 14, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, March 7th 2022
This study estimates that prescreening with a 500 blood test could reduce by half both the cost and the time it takes to enroll patients in clinical trials that use PET scans. Screening with blood tests alone could be completed in less than six months and cut costs by tenfold or more, the study finds. Known as Precivity AD, the commercial version of the test is marketed by C2N Diagnostics. The current study shows that the blood test remains highly accurate, even when performed in different labs following different protocols, and in different cohorts across three continents. xCT Knockout Modestly Extends Life in M...
Source: Fight Aging! - March 6, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, February 21st 2022
In conclusion, clinical trials targeting aging in humans have shown promising but limited results on biomarkers so far. Mycobacterium Vaccae Immunization as an Anti-Inflammatory Strategy https://www.fightaging.org/archives/2022/02/mycobacterium-vaccae-immunization-as-an-anti-inflammatory-strategy/ In today's open access paper, researchers discuss immunization with Mycobacterium vaccae as an approach to reduce the inflammatory overactivity of the aged immune system. Researchers have made some initial inroads into studying the way in which this bacteria can alter the function of the immune system, and here...
Source: Fight Aging! - February 20, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

A Hypothetical Project: the Fast Track to Partial Reprogramming in Human Volunteers
In a recent post, I suggested that is practical and useful for small organizations to run low-cost clinical trials in large numbers in order to build physician support for treatments for aging that should, by rights, already be in the clinic. The senolytic treatment of dasatinib and quercetin is the most obvious candidate, given its low cost, availability for off-label use, broad, large, and reliable benefits in animal models of aging and age-related disease, and human evidence for efficacy in clearing senescent cells to a similar degree as it does in mice. Today I'll propose a different angle on early, small trials...
Source: Fight Aging! - February 14, 2022 Category: Research Authors: Reason Tags: Activism, Advocacy and Education Source Type: blogs

Fight Aging! Newsletter, February 14th 2022
In conclusion, this first examination of the effects of age and the ageing process on the small intestinal microbiome demonstrates that the duodenal microbiome changes with increasing age, with significant decreases in duodenal microbial diversity due to increased prevalence of phylum Proteobacteria, particularly coliforms and anaerobic taxa. Given the key roles of small intestinal microbes in nutrient absorption and host metabolism, these changes may be clinically relevant for human health during the ageing process. Naked Mole Rats Exhibit Minimal Cardiac Aging https://www.fightaging.org/archives/2022/02/naked...
Source: Fight Aging! - February 13, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, January 24th 2022
In conclusion, senolytic drugs have shown promising results in the elimination of senescent cells and in alleviating various diseases in animal models. However, in patients, there is a paucity in data on the efficacy and safety of senotherapeutics from clinical trials, including systemic effects and side-effects. In this regard it is important to assess the specificity of senolytics in killing targeted senescent cells and their cytotoxic effects, to identify reliable markers for intervention responses, to elucidate interactions with comorbidities and other drugs, and to standardise administration protocols. FOXO3...
Source: Fight Aging! - January 23, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Temporary Chimeric Antigen Receptor T Cells Produced in the Body via mRNA Gene Therapy
Chimeric antigen receptors applied to T cells, known as CAR-T therapies, are expensive. Isolating a patient's T cells, culturing them, engineering them, and then returning them to the body is an undertaking, particularly when it must be carried out with the very high level of reliability and quality control required by regulators. CAR-T therapies do well in attacking many types of cancer, but can have side-effects due to the lasting presence of engineered immune cells that have become too zealous. Few chimeric antigens are completely specific for cancer, and other cells will be destroyed as well. The approach noted here is...
Source: Fight Aging! - January 17, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, January 3rd 2022
In this study, we showed that the iPaD (inducing Plagl2 and anti-Dyrk1a) lentivirus substantially rejuvenated the proliferative and neurogenic potential of NSCs in the aged brain. Clonal analysis by a sparse labeling approach as well as transcriptome analysis indicated that iPaD can rejuvenate aged NSCs (19-21 mo of age) to a level comparable with those at 1 or 2 months of age and successfully improved cognition of aged mice. Once rejuvenated and activated by iPaD, aged dormant NSCs can generate, on average, 4.9 neurons but very few astrocytes in 3-week tracing. Furthermore, these activated NSCs were maintained for ...
Source: Fight Aging! - January 2, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

A Look Back at 2021: Progress Towards the Treatment of Aging as a Medical Condition
Well, here we are again, at the end of another pandemic year, a year older and - hopefully - a year wiser and more knowledgeable. I said all that really needs to be said on the topic of COVID-19 as an age-related condition at the end of last year. We might hope that, given widespread vaccination, the pandemic will become a topic of diminishing importance as the year ahead progresses, even given the present round of variants, fears, and reintroduction of restrictions. Advocacy for Aging Research Have we finally made significant progress in convincing the world that aging is the cause of age-related disease, th...
Source: Fight Aging! - December 31, 2021 Category: Research Authors: Reason Tags: Of Interest Source Type: blogs

Fight Aging! Newsletter, December 27th 2021
We report that whereas microglia are characterized by marked gene-level alterations related to negative regulation of protein phosphorylation and phagocytic vesicles, astrocytes show activation of enzyme- or peptidase-inhibitor signaling after detectable changes in BBB permeability. We also identify several genes enriched in these pathways that are notably altered after BBB breakdown. Our data reveal that microglia and astrocytes play an active role in maintaining BBB stabilization and corralling infiltrating cells, and thus might potentially function in ameliorating the lesions and neurologic disabilities in CNS diseases....
Source: Fight Aging! - December 26, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, December 20th 2021
In conclusion, the low dose, prolonged angiotensin II exposure is associated with the induction of senescence in kidneys and the promotion of an inflammatory microenvironment through both secreted factors and immune cells. Endothelial cells appear to be a major cell type impacted. The elimination of senescent cells in the INK-ATTAC transgenic model prevents these effects of angiotensin II and reveals a novel pathophysiologic mechanism amenable to targeting by senolytic drugs in development. CYTOR Upregulation as a Path to Improved Muscle Function in Later Life https://www.fightaging.org/archives/2021/12/cytor-u...
Source: Fight Aging! - December 19, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, December 13th 2021
In conclusion, there is a good amount of pre-clinical and clinical data showing a strong positive correlation between reduction of senescent cells frequencies and functional improvement of skin. Whether senescence of skin cells makes a significant causal contribution to skin ageing can still not be conclusively decided, however. Nonetheless, there is strong evidence existing today to assume that better understanding of cell senescence in skin may lead to a breakthrough in interventions into skin ageing. Isomerization of Tau May be Involved in Alzheimer's Disease https://www.fightaging.org/archives/2021/12/isome...
Source: Fight Aging! - December 12, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, November 22nd 2021
This study nicely illustrates the importance of the cellular metabolic state of myeloid cells: it highlights that not only the availability of glucose, but also its channeling into different pathways (glycolysis versus glycogen synthesis) contributes to maintaining proper myeloid function. On the Ability of Redundant Blood Vessels to Lower Cardiovascular Mortality https://www.fightaging.org/archives/2021/11/on-the-ability-of-redundant-blood-vessels-to-lower-cardiovascular-mortality/ A few strategies offer the possibility of growing additional redundant blood vessels, though this is far from rigorously pr...
Source: Fight Aging! - November 21, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, November 8th 2021
In conclusion, in less common and visible cardiovascular diseases, it is crucial to recognize substantial progress and achievement, given that penetration of such information into clinical practice and the patient community can be inconsistent. Diseases such as hypertrophic cardiomyopathy, pulmonary arterial hypertension, and ATTR cardiac amyloidosis, once linked to a uniformly adverse prognosis, are now associated with the opportunity for patients to experience satisfactory quality of life and extended longevity. VitaDAO, a Novel Approach to Crowdfunding Life Science Research https://www.fightaging.org/archive...
Source: Fight Aging! - November 7, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs