Read More at Fight Aging! Today’s open access paper mounts an interesting argument, based on the use of a large data set for phenotypic aging in mice. They looked at transcriptomic and proteomic data for a sizable number of genes in a variety of different tissues, then grouping these into phenotypes by related function, or relation to specific age-related declines. Differences in expression by age in these phenotypic groups of genes were observed directly in mice and in human data sets. The researchers then looked the effects on phenotypes of a few very well studied interventions widely thought to slow aging in mice: growth hormone signaling inhibition, mTOR inhibition, and intermittent fasting. The authors argue, based on their data, that these interventions are essentially compensatory rather than age-slowing, in that they appear to be changing phenotypes (mostly for the better)…
Further Discussion of the Poor Evidence For Metformin to Even Mildly Slow Aging`
Read More at Fight Aging! The problem with metformin as a drug to slow aging is that the evidece to support that use is very poor. In animal studies, the results are very unreliable, and the Interventions Testing Program found no effect in its highly overengineered studies. Further, the existing human data is not supportive, taken as a whole. Even if we did want to cherry pick the better data and be hopeful, the effect size compares unfavorably with that achieved through regular exercise, and further appears to be only achieved in people with the abnormal metabolism associated with obesity and diabetes. All of the work that was done to convince the FDA to endorse the TAME human clinical trial to test the ability of metformin to slow aging is useful, but the resulting agreement on trial structure should be…
Investigating the Ability of Type 2 Diabetes Treatments to Modestly Slow Aging Extends to SGLT-2 Inhibitors
Read More at Fight Aging! There is something of a trend towards picking over the landscape of type 2 diabetes medication in search of therapies that can modestly slow aging, at least in animal models. If metformin is anything to go by, we shouldn’t be at all optimistic that this will result in useful outcomes in humans. “Useful” in this context means reliable gains in late life health and life expectancy in metabolically normal people, where those gains are larger than those that can be achieved with exercise, and with minimal side-effects. Otherwise, this seems like time and effort that could be directed to more productive areas of research and development. Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none…
Towards the Widespread Use of Gerotherapeutic Drugs to Slow Aging
Read More at Fight Aging! Many compounds, small molecules, plant extracts, and so forth, have been found to modestly slow aging in mice. Given accumulating evidence from animal studies and human clinical trials, and that a sizable fraction of these compounds are already approved by regulators for other uses, or otherwise readily available, it is inevitably the case that physicians and the population at large will begin make use of these treatments in increasing numbers. This will happen, sometimes ahead of the science, sometimes behind it, sometimes to little benefit to patients, sometimes with enough of a benefit to matter. Navigating the options will become a great deal harder than it was, as we transition from an era in which little to nothing could be done to change the pace of aging, to one in which there are many options,…
Discussing the State of the TAME Clinical Trial, Metformin to Slow Aging
Read More at Fight Aging! The TAME clinical trial, still not started, intends to assess the ability of metformin to marginally slow aging in humans. Back at the start of this initiative, it required a long process of negotiation on the part of the trial organizers with the FDA to produce an endpoint that was agreed upon to sufficiently represent aging. To my mind, the TAME trial initiative has already achieved what needs to be achieved: to get the FDA to agree that there is a way to run trials to treat aging. One doesn’t actually need to run the trial, and there is in fact little point in running the trial. Metformin is almost certainly a marginal treatment, and attention should be directed instead towards senolytics and other approaches that have much, much better animal data to support their…