Highlights

For individuals interested in biohacking their way to a longer lifespan, the question of when to start using an aging intervention, such as rapamycin or metformin, is a significant concern that warrants careful consideration. While research on this matter has not yet yielded solid recommendations for when to begin aging interventions, some patterns regarding how mammals age may provide valuable insights. Along those lines, through their research on aging interventions applied early in life in rodents, scientists may one day determine which aging interventions are most beneficial when taken during the earlier life stages in humans.

This intriguing idea relates to scientists’ observation of an inverse correlation between the lifespans of mammal species and their rate of development. In other words, mammalian species that develop at a slower rate tend to live longer. This inverse correlation between the pace of development and lifespan has prompted Bartke and colleagues from Southern Illinois University to investigate the effects of aging intervention applications early in life on lifespan in mice, as published in Aging and Disease. Delving into this realm of research may provide insight into which life stages to begin taking aging interventions for lifespan optimization in humans.

An Inverse Correlation Between the Pace of Development and Lifespan

Intriguingly, based on the inverse correlation between the pace of development and lifespan, Bartke and colleagues arrived at the hypothesis that early life may serve as a time window for interventions that can modify the aging trajectory and impact lifespan. Moreover, the theory of developmental origins of adult health and disease (DOHAD) supports their new hypothesis. The DOHAD originated from studying individuals whose mothers were exposed to starvation during pregnancy. These individuals, exposed to low-calorie and low-protein diets while in the womb, had an increased risk of obesity, cardiovascular disease, and diabetes. The increased risks for these age-related conditions in these individuals support the notion that early life conditions influence aspects of aging in later years.

In addition to studying individuals whose mothers were exposed to starvation, other research has revealed that adverse childhood experiences, like abuse, famine, and lower socioeconomic position, are associated with an increased risk of cardiovascular disease, diabetes, and other age-related conditions later in life. This data supports the notion of adverse early life conditions during certain periods of development impacting risks for age-related conditions at later stages of life and, perhaps, aspects of aging more generally. This notion led Bartke and colleagues to ponder whether they could flip the script and use aging interventions during earlier life stages to improve aspects of aging and longevity.

Preclinical Trials Testing Aging Interventions In Early Life

As such, the researchers analyzed preclinical studies done with mice, which utilized various aging interventions, like rapamycin and metformin, to get a better grasp on whether scientists may one day apply aging interventions at earlier life stages in humans. Their findings generally support that treatment with certain aging interventions during early life confers significant effects on lifespan extension.

More specifically, rapamycin, an immunosuppressant drug used to prevent organ transplant rejection that some have repurposed to promote longevity, has been applied during development in mice. Injecting mice with rapamycin between 4 and 30 days after birth (roughly equivalent to between the ages of 5 and 13 in humans) modulated development and reduced body and organ size and significantly extended lifespan. This finding underscores the potential of using aging interventions in early life stages to impact lifespan.

The chemical structure of rapamycin
(The chemical structure of rapamycin | STEMCELL Technologies)

In a similar vein, mice treated with the diabetes drug metformin, which has also been repurposed to promote longevity, during midlife did not extend lifespan. However, treating mice at the third, fifth, and seventh days after birth (roughly equivalent to ages three, five, and seven for humans) significantly extends lifespan for males. Such findings add support to the notion that aging interventions may reap more pro-longevity benefits when applied early in life.

Metformin tablets
(Metformin tablets | My Health Explained)

What This Means for Humans

What this analysis of studies on the application of aging interventions early in life means for humans remains debatable. Since aging interventions applied early in life, during periods of development, yield the most significant effects on lifespan at times, this suggests that interventions during developmental periods have a significant effect.

All the same, there are risks associated with starting certain aging interventions early and taking them for long periods. For example, long-term rapamycin use is associated with risks like metabolic dysregulation, weakened immunity, and kidney problems. Furthermore, long-term metformin use is associated with side effects like numbness, tingling, and memory problems. As such, individuals interested in using aging interventions before old age should consult with a physician before doing so.

Since development before puberty is a crucial period for shaping healthy, functional human adults, applying aging interventions during this period of life in humans remains, in large part, highly controversial. Bartke and colleagues’ analysis of studies does, however, raise the question of whether beginning aging interventions in earlier adult years, such as in the 30s, may modulate aging pathways to optimize longevity. However, only future human trials measuring aging interventions’ effects on things like metabolic parameters and body weight composition will provide better insight as to when to start taking interventions.