It’s Never Too Late: Taking Anti-Aging Compounds Early or Late in Life Thwarts Physical Decline and Heart Aging, Study Shows

Highlights: 

• Regardless of whether treatment started early in life (similar to a 25-year-old human) or later (similar to a 52-year-old human), by 22 months of age (similar to a 65-year-old human), all mice treated with acarbose or rapamycin saw enhancement in motor function, endurance capacity, and coordination.
• Early or late-life treatment with acarbose or rapamycin mitigates cardiac hypertrophy (enlargement) in aged mice. 

Acarbose (ACA) and rapamycin (RAP) are two compounds at the forefront of anti-aging interventions, with multiple preclinical studies demonstrating their ability to extend lifespan and ameliorate several features of aging, like physical dysfunction and cardiac abnormalities. However, in many of these studies, treatment was commenced either early in life or late into adulthood, leaving scientists unsure about the optimal time for initiating treatment to promote healthier aging and prolong lifespan. 

Now, in a new study published in the Journals of Gerontology: Biological Sciences, researchers from the University of Michigan explored the effects of early and late-life intervention with ACA and RAP on physical function and cardiac health. Herrera and colleagues showed that early or late-life treatment with ACA or RAP significantly boosts motor function, endurance capacity, and coordination in aged (22 months) mice. What’s more, the investigators found that cardiac hypertrophy was decreased in aged mice following early and late-life treatment with ACA and RAP, indicating that both treatments delay cardiac aging. 

Acarbose and Rapamycin Enhance Physical Function

As we surpass our youthful state, coordination, strength, and endurance whittle away, driving physical impairment and increasing frailty. Uniquely, ACA and RAP are linked to thwarting these debilitating aspects of aging; however, researchers have yet to differentiate their effects when commenced at different stages of life. Furthermore, researchers have yet to elucidate whether treatment affects males and females differently. With this in mind, Herrera and colleagues assessed whether physical function in aged male and female mice could be improved with ACA or RAP treatment starting at 4 months (early life) of age or 16 months (late life) of age. 

To evaluate physical function, the investigators employed the rotarod acceleration test, which assesses the mouse’s ability to maintain balance and coordination while walking or running on a rotating rod that gradually increases in speed. The results revealed that both early and late-life treatment with ACA and RAP significantly increased the average time spent on the rotating rod, indicating enhanced motor coordination and balance. However, RAP treatment starting at 16 months only reached statistical significance in males when compared to untreated aged mice (controls). 

Similar results were seen when the investigators measured endurance through the rotarod endurance test, where the speed of the rod was kept constant. While early and late-life treatment with ACA significantly increased the endurance capacity of both males and females, early and late-life RAP treatment reached statistical significance only in males, further suggesting a sex-specific effect with RAP. Taken together, the findings demonstrate that early and late-life treatment with ACA or RAP successfully delays age-related physical decline. 

Acarbose and Rapamycin Ameliorate Heart Aging 

In addition to ACA and RAP having profound effects on physical function, they’ve also been shown to influence features of cardiac aging, particularly cardiac hypertrophy, which is known to exacerbate cardiac dysfunction. As previously mentioned, there remains a significant knowledge gap regarding the optimal time for initiating treatment. Thus, the Michigan researchers evaluated whether early or late-life treatment with ACA or RAP is more suitable to delay cardiac hypertrophy.

Parallel to the physical function data, both early or late-life treatments with ACA were equally successful in male and female mice, significantly decreasing cardiac hypertrophy. By the same token, cardiac hypertrophy was attenuated with early or late-life treatments with RAP, affecting males and females similarly. Accordingly, the findings suggest that early or late-life treatment with ACA or RAP is equally effective at delaying cardiac aging. 

Timing Isn’t Everything 

It’s clear that early or late-life treatment with ACA and RAP helps protect against age-related physical and cardiac abnormalities. Although there appears to be a sex-specific effect when it comes to improving physical function with RAP treatment starting at a later stage in life, with beneficial effects only observed in male mice. Interestingly, this sex-specific finding conflicts with previous lifespan studies showing that late-life rapamycin treatment exerts more pronounced life-extending effects in females than males, highlighting the need for future studies to differentiate the sex-specific effects of late-life RAP treatment.

It’s important to note that the sex-specific differences in physical function did not carry over to the changes in cardiac hypertrophy. In fact, both early and late-life treatment with ACA or RAP produced similar beneficial effects in male and female mice, implying that starting treatment later in life can still mirror the heart-boosting effects of life-long treatment with ACA or RAP. This finding is especially important, as it emphasizes the fact that it’s never too late to implement interventions that can help prolong longevity and improve overall well-being in old age. While more research needs to be done, anti-aging compounds like ACA and RAP could provide a means of improving physical health and reversing heart aging. Notably, both of these compounds are prescription drugs, so make sure to consult with a physician before starting treatment.