Improved Physical Function in Old Mice Treated with Rapamycin, Acarbose, and Phenylbutyrate

It is quite rare for researchers to attempt combined treatments, unfortunately. The panoply of calorie restriction mimetics and other approaches to gently upregulate stress responses are individually not all that impressive, and it remains unclear as to which of them can be stacked for greater effect. In the treatment of aging, even the better approaches that produce actual and rapid rejuvenation, such as senolytic therapies to destroy senescent cells, will have to be stacked with one another. There are many different contributing causes of aging. Here, researchers report that a combination therapy carried out for a few months in aged mice produces improvements of 20-40% in physical function. That duration corresponds, very roughly, to a decade or more of sustained treatment in old humans.

Loss of physical performance, as seen in humans by decreased grip strength and overall physical fitness, is generally accepted to be a consequence of aging. Treatments to delay or reduce these changes or increase resilience to them are generally not available. In this preliminary study, 20-month-old male and female C57BL/6 mice were given either a standard mouse diet or a formulated mouse diet containing rapamycin (14 ppm), acarbose (1000 ppm), and phenylbutyrate (1000 ppm), or a diet containing one half dose of each drug, for 3 months. At the end of the study, performance on a rotarod and grip strength test was compared.

Rapamycin blocks mTOR, a protein shown to integrate signals from growth factors and nutrients to control protein synthesis. The anti-aging effect of downregulating mTOR was confirmed by the NIA Intervention Testing Program showing that rapamycin extended lifespan in mice. Arcabose is a popular type 2 diabetes medication used for glucoregulatory control, and it also increases mouse lifespan. Phenylbutyrate is clinically approved as an ammonia scavenger for urea cycle disorders in children, and is also an inhibitor of histone deacetylase. In aging mice, it enhances physical and cognitive performance.

In general, mice fed the full dose drug cocktail diet performed better on these assays, with significant improvements in rotarod performance in females fed the full dose cocktail and in grip strength in males fed the full dose cocktail, and females fed the low dose cocktail. These observations provide support for the concept that short term treatment with a cocktail of drugs that targets multiple aging pathways can increase resilience to aging, and suggests that this prototype cocktail could be part of a clinical therapeutic strategy for delaying age-related loss of physical performance in people.



40% in mice can give how's to translate 10-15% to humans. It won't make the 70 new sixties but can mean delaying disability by 2-4 years. Nothing too sniff at

Posted by: Cuberat at February 8th, 2022 8:54 AM


Do you think in countries without human rights, that they are much further along?

Posted by: Person1234 at February 8th, 2022 9:27 AM

I wonder how this would compare with actual calorie restriction in mice.

Posted by: GREGORY S SCHULTE at February 8th, 2022 11:31 AM

Probably an extreme CR would yield better results. Intermittent feeding and moderate CR , as far as I remember increased the lifespan 10 to 20% in mice. If I make the leap and image that 20% of improved function is very similar to increased lifespan of 20%( and we all know it is not) then the cocktail will as good as intermittent fasting or some moderate CR. Not too bad

Posted by: Cuberat at February 8th, 2022 5:45 PM

The countries without human rights happen to be much more disfunctional in so many ways than OECED ones that there's no way

On top of that, to advance a longevity research you need to care about the old folks. And yet at the same time to not care about side effects.

If you take, for example, Singapore, it has some human rights quite reduced. But the role of law is quite strong, and they are quite big in the safety.
So while you cannot bue chewing gum there, they will not condone any unethical experiments.

On the other end, we can look at Somalia. With enough finding a super villain scientist could set up a shop there and do all kinds of experiments. But as since the role of law is non-existent the above mentioned evil scientist will have his lab pillaged, supplies stolen and robbed.

Posted by: Cuberat at February 8th, 2022 6:00 PM

Mice fed BHT from birth lived 40% longer, according to a study done in the early 1970s. Why is that ignored?

Posted by: Tom at February 13th, 2022 3:12 PM

I remember in 1970 I read that rats fed a diet supplemented with 1% BHT lived 10% longer. This must not be said, as it would interfere with the advertising of aging accelerators that are running in the media.

Posted by: Jan Omasta at February 13th, 2022 10:21 PM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.