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There is far too much incrementalism in the present research and development of therapies to treat aging. Much of the field is engaged in mimicking calorie restriction or repurposing existing drugs that were found to increase mouse life span by a few percentage points. This will not meaningfully change the shape of human life, but nonetheless costs just as much as efforts to achieve far more. If billions of dollars and the efforts of thousands of researchers are to be devoted to initiatives to treat aging, then why not pursue the ambitious goal of rejuvenation and adding decades to healthy life spans? It is just as plausible. There are just as many starting points and plausible research programs aimed at outright rejuvenation via repair of molecular damage, such as those listed in the SENS approach to aging, as there are aimed at achieving only small benefits in an aged metabolism. The heavy focus on incremental, low yield programs of research and development in the present community is frustrating, and that frustration is felt by many.
As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans. With space travel, scientists and engineers couldn't know what it would take to get to the moon. They had to extrapolate from theory and shorter-range tests. Perhaps with aging, we need a similar moonshot philosophy. Like the moon once was, we seem a long way away from provable therapies to increase human healthspan or lifespan. This review therefore focuses on radical proposals. We hope it might stimulate discussion on what we might consider doing significantly differently than ongoing aging research.
A less than encouraging sign for many of the lifespan experiments done in preclinical models, namely in mammals such as mice, is that they have modest effect sizes, often only having statistically significant effects in one of the genders, and often only in specific dietary or housing conditions. Even inhibiting one of the most potent and well-validated aging pathways, the mechanistic target of rapamycin (mTOR) pathway has arguably modest effects on lifespan - a 12-24% increase in mice. This is all to ask, if the mTOR inhibitor rapamycin is one of the potential best-case scenarios and might be predicted to have a modest effect if any (and possibly a detrimental one) in people, should it continue to receive so much focus by the aging community? Note the problems in the aging field with small and inconsistent effects for the leading strategies aren't specific to rapamycin.
Treating individual aging-related diseases has encountered roadblocks that should also call into question whether we are on the optimal path for human aging. Alzheimer's is a particularly well-funded and well-researched aging-related topic where there are still huge gaps in our understanding and lack of good treatment options. There has been considerable focus on amyloid beta and tau, but targeting those molecules hasn't done much for Alzheimer's so far, leaving many searching for answers. The point is when we spend collectively a long time on something that isn't working well, such as manipulating a single gene or biological process, it should seem natural to consider conceptually different approaches.
Link: https://doi.org/10.3233/NHA-190064
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source https://www.fightaging.org/archives/2021/01/moonshots-for-the-treatment-of-aging-less-incrementalism-more-ambition/
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