Combinations of Approaches to Slow Aging are Not Well Explored

Scores of distinct ways to modestly slow aging in short-lived species have been demonstrated in the laboratory over the past decades. Many are redundant, influencing the same underlying mechanism, but others produce effects on the operation of cellular metabolism that are different enough to be synergistic. Unfortunately the research community does very little work on combined therapies; this true for all fields of medicine, not just aging. This is perhaps partially the culture of science, and partially the consequence of heavy handed regulation and intellectual property law. The financial incentives at all level of research and development make it harder to set out to combine therapies or potential therapies than to just work on something else.

Still, some efforts take place, though they fall far short of the "let's try everything at once" concepts that may make sense from a practical point of view. Combining every known method of slowing aging will at the end of the day still fail to produce rejuvenation, as the underlying damage that causes aging is not repaired to any significant extent, but it may well produce enough of a benefit to be worth trying, given that the approaches already exist in some form.

The idea behind the study was to test whether combinations of drugs known to extend healthspan and/or lifespan in animal models could work in synergy and produce even more pronounced effects. The team chose rifampicin, rapamycin, psora-4, metformin, and allantoin. Some of these, namely rapamycin and metformin, are well-known for their connection to lifespan, though their original purposes were somewhat different - rapamycin is used to prevent organ transplant rejection, whereas metformin is a 50-year-old, off-patent drug used to treat type 2 diabetes.

The researchers used C. elegans nematodes as test subjects; their intent was to see which drug combinations, if any, would provide the largest health and lifespan benefits without causing toxicity. While some combinations did turn out to be toxic or no more effective than the single drugs, others proved significantly more effective when used together; In particular, the combination of rapamycin, rifampicin, and allantoin achieved an 89% extension of mean lifespan, whereas rifampicin, psora-4 and allantoin resulted in a 96% increase of mean lifespan - all of which were without any toxicity.

It is also very important to note is that all treated worms of all ages didn't just live longer; rather, they spent a larger portion of their extra lifespan in good health, which constitutes even more evidence that interfering with the aging processes is a promising avenue to obtain significant health gains. Interestingly, comparable effects were observed when testing similar drug cocktails in fruit flies; nematodes and fruit flies are significantly far apart, evolutionarily speaking, which, according to the researchers, suggests that the aging mechanisms targeted by these drug combinations must trace all the way back to an ancient common ancestor of the two species. This is good news for humans, as it increases the likelihood that similar interventions might work in us as well.

Link: https://www.leafscience.org/treating-multiple-aging-pathways-simultaneously-extends-healthy-lifespan-of-nematodes/

Comments

Can somebody post a link to the full study that isn't hidden behind a paywall?

Posted by: DdR at October 31st, 2018 9:05 AM

Just go to Sci-Hub and put the name of the paper in and bingo!

Posted by: Steve Hill at October 31st, 2018 12:03 PM

It is an interesting study. However, I am not sure that it translates smoothly to humans but it is a starting point.

Posted by: Cuberat at October 31st, 2018 3:32 PM

Interesting. I always wondered about rifampicin, known to some for possible healthspan/lifespan effects but more known as a potent antibiotic to treat in particular tuberculosis and a range of non-tuberculosis mycobacteria (NTM) such as M. avium and M. kansasii. There are hepatoxicity effects as, for these conditions, treatments are long, typically 12-18 months, and in combination with 2 or 3 more antibiotics to avoid resistance.

Posted by: albedo at November 4th, 2018 11:47 AM

"It is an interesting study. However, I am not sure that it translates smoothly to humans but it is a starting point."

Yes exactly...the same could be said about mouse studies. I hope George Church's approach of marketing anti-ageing techniques first as a treatment for pets (dogs) bears fruit. Don't know what he is actually planning on using as a treatment(s) perhaps something similar to what is being discussed here, at least initially.

Posted by: Tim at November 4th, 2018 6:15 PM

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