The Strategy of mTORC1 Inhibition Fails a Phase III Trial

The worst possible outcome when developing a clinical therapy is not an early failure. It is a late failure, in the final and most expensive phase III clinical trial, in which the therapy interacts with a sizable patient population, and after a great deal of time and funding have been devoted to the program. This result is far more likely for therapies based on mechanisms that have smaller rather than larger effect sizes, and where that smaller effect size varies from individual to individual for reasons that are not well understood - something that describes all too much of the past few decades of efforts to treat age-related disease. Unfortunately this worst case phase III failure just happened to resTORbio's mTORC1 inhibitor RTB101, in tests of its ability to improve immune function and reduce the burden of infection in later life. The inhibition of mTOR, and specifically only the mTORC1 protein complex in order to reduce side-effects resulting from inhibition of mTORC2, is one of a range of potential approaches demonstrated in animal models to modestly slow aging via upregulation of cellular stress response mechanisms. It affects some of the same processes as calorie restriction and exercise. Another way of looking at it is that it pushes metabolism into a state that makes it incrementally more resilient to the accumulated damage of aging. However, all such strategies examined to date perform far better in short-lived species than in long-lived species, a situation...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
James Peyer, formerly of Apollo Ventures and now at the larger Kronos BioVentures, has a range of interesting views on the new and growing longevity biotechnology industry. Apollo Ventures was one of the earlier longevity-focused funds to emerge from the comparatively small community of scientists, patient advocates, and investors enthusiastic to accelerate progress towards the treatment of aging as a medical condition. The presentation here was given earlier this year at the Ending Age-Related Diseases conference organized by the Life Extension Advocacy Foundation. In the matter of creating new medical therapies, t...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Publication date: Available online 18 April 2019Source: Journal of Sport and Health ScienceAuthor(s): Xin Luan, Xiangyang Tian, Haixin Zhang, Rui Huang, Na Li, Peijie Chen, Ru WangAbstractA growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy. Because each sport has its own set of characteristics and physiological complications that tend to appear during exercise training, the effects and underlying mechanisms of exercise remain unclear. Thus, the first step in probing exercise effects on different diseases is the s...
Source: Journal of Sport and Health Science - Category: Sports Medicine Source Type: research
This study suggests that advantages and disadvantages vary by environment and diet, however, which might explain why evolution has selected for multiple haplogroups rather than one dominant haplogroup. This is all interesting, but none of it stops the research community from engineering a globally better-than-natural human mitochondrial genome, and then copying it into the cell nucleus as a backup to prevent the well-known contribution of mitochondrial DNA damage to aging. Further, nothing stops us from keeping the haplogroups we have and rendering the effects of variants small and irrelevant through the development...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion of Mitochondrial Hormesis as an Approach to Slow Aging Cornelis (Cees) Wortel, Ichor Therapeutics Chief Medical Officer, on Rejuvenation Research and Its Engagement with the Established Regulatory System An Interview with a Programmed Aging Theorist An Interview with Reason at the Life Extension Advocacy Foundation An Interview on Mitochondrial Damage and Dysfunction in Aging An Interview with Vadim Gladyshev on Research into the Causes of Aging An Interview with Jim Mellon, and Update on Juvenescence A Lengthy Interview with Aubrey de Grey of the SENS Research Foundation An Interview with Peter de Keize...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
CONCLUSIONS: Almost half of the people who died at home are SCP although only two out of three are identified as such. Cancer is the most frequent SCP disease and the easiest one to identify, largely affecting men. Three out of four people with dementia died without being identified as PC, and they are mainly women. PMID: 30277226 [PubMed - as supplied by publisher]
Source: Anales del Sistema Sanitario de Navarra - Category: General Medicine Authors: Tags: An Sist Sanit Navar Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
DISCUSSION: Overall, the literature supports beneficial pleotropic effects of statin use in contrast-induced nephropathy, head injury, Alzheimer's and Parkinson's disease, nuclear cataract, prostate cancer, infection management, and spinal cord injury. Further investigation is warranted, and randomized clinical trials are needed to confirm the clinical utility suggested by the reported studies included in this meta-analysis. PMID: 30033872 [PubMed - as supplied by publisher]
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research
Abstract The majority of leisure-time is spent in sedentary behaviors such as television viewing. Studies have documented that prolonged leisure-time sitting is associated with higher risk of total, cardiovascular disease, cancer, and "all other causes" of mortality, but few have examined the "other" causes of death in detail. To examine associations of leisure-time sitting with risk of specific causes of death, data were analyzed from the CPS-II Nutrition Cohort, a prospective U.S. cohort including 127,554 men and women who were free of major chronic disease at study entry and among whom 48,78...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
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