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  • Writer's pictureNick Allen

Drugs for longevity?

We talk often about lifestyle strategies for improving lifespan and healthspan, but what if there was a shortcut? While a pill to make you live longer sounds like sci-fi, simple interventions to extend life are being actively researched in animals. Perhaps the most notable work on this front comes from the Interventions Testing Program (ITP), a multi-site operation from the National Institute on Aging (NIA).


The ITP has studied dozens of compounds for anti-aging benefit in mice and continues to accept recommendations from the scientific community. Each compound selected is tested under a rigorous protocol at 3 distinct academic centers. The benefits of this program are multiple. The obvious one is that any compound shown to successfully extend lifespan in mice may be able to do so in humans as well. Beyond this, however, the results can teach us a lot about the aging process and how to delay the onset of disease.


Let’s take a look at some of the successes and failures of the ITP thus far. For now we’ll stick to the key takeaways; some of these molecules warrant a much more detailed discussion and will be the focus of future material.


Resveratrol, the sirtuin activator found in red wine, was unsuccessful in extending lifespan. Following the advice of David Sinclair, who wrote the original paper proposing resveratrol as a longevity agent, the ITP tested two doses of the molecule. The recommended doses were equivalent to a human consuming hundreds of bottles of red wine per day, and still they failed to show a longevity benefit in either male or female mice.


Rapamycin, a TOR inhibitor, was overwhelmingly effective even when given to older mice. Technical difficulties led to the delay of rapamycin administration until the mice were 20 months old, the equivalent of 60 years in humans. Despite this late start, the median lifespan increased 13% in male mice and 20% in female mice. A repeat of this study with an earlier start (9 months of age) demonstrated even better results (Figure 1).


Figure 1: The proportion of female mice surviving over time with or without rapamycin added to the diet (concentration of 14 ppm, initiated at 9 months of age).


Metformin is a drug previously discussed on the blog, where we outlined its mechanisms of TOR inhibition and AMPK activation. This drug has shown promise to the point that there is a massive six-year, 3,000+ patient trial currently in progress to study the effects of metformin on aging. It has also been shown consistently to lower hepatic (liver) glucose output, which is why it is already used in treatment for diabetes. Surprisingly, the ITP trial of metformin was unsuccessful in expanding lifespan. However, the combination of metformin and rapamycin worked even better than rapamycin alone. As you’ll see through the rest of this post, drugs involved with glucose regulation commonly show up in longevity studies.


Another example is acarbose, a drug that slows the breakdown and absorption of carbohydrates in the gut. The ITP trial showed that this drug increased lifespan preferentially in males. While the compound led to a 5% increase in median lifespan in females, it contributed to a 22% increase in median lifespan in male mice. The thought here is that acarbose limits the post-prandial blood sugar spike, something we’ve repeatedly discussed as being damaging to health.


Canagliflozin, from the SGLT-2 inhibitor class of drugs, improved longevity in male mice (median survival increased 14%) but did not change female lifespan significantly. Like acarbose and metformin, this is a drug currently used in diabetic patients. While these drugs all have different mechanisms, canagliflozin is similarly effective in lowering blood sugar in humans and mice.


These are just a few of the important results from the ITP, which continues to churn out new data every year. As you can see, these studies provide valuable information to the fields of aging and disease prevention. For example, seeing multiple blood sugar-lowering drugs in the success category makes me even more confident that blood sugar control is crucial to health. While it may be quite some time before these drugs are used by humans for lifespan extension, we have other tools (diet, exercise, sleep, and stress management) to control blood sugar and mimic the effects of these compounds.


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