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.