·       Historically, longer life expectancies arise from lower infant and juvenile death rates.
·       But the rate of aging has remained mostly constant even though life expectancies have improved.
·       To substantially increase future human life expectancy, we need to reduce the aging rate with an anti-aging medical breakthrough.

Although our average life expectancy has steadily increased since the mid-1800s, these gains have resulted from postposing deaths to later ages and not improving the aging rate. In other words, even though fewer people die at an early age, those that live longer aren’t aging more slowly. This has led some researchers to propose that a fixed aging rate limits further increasing lifespan extension, or what’s called the ‘invariant rate of aging’ hypothesis. 

By analyzing the lifespan trajectory of humans and other primates, Alberts and colleagues from Duke University show evidence strongly supporting the existence of these constraints to aging rates in an article published in Nature Communications. This study shows that life expectancy rises as more infants and juveniles survive, but our aging rate is generally constant, putting a cap on the maximum number of years we live. By confirming the ‘invariant rate aging’ proposal, Alberts and colleagues propose that only with age-slowing medical strategies can we make substantial improvements to future life expectancy.

“Life expectancy has increased dramatically and still does in many parts of the world. But this is not because we have slowed our rate of aging; the reason is that more and more infants, children, and young people survive and this brings up the average life expectancy,” said Fernando Colchero, a lead author of the study, in a press release.

Humans and Primates Have Invariant Aging Rates 

To see if human and non-human primates share any universal aging patterns, Alberts and colleagues compared aging trajectories from humans and our closest relatives, 30 species of primates.

“We observe that not only humans, but also other primate species exposed to different environments, succeed in living longer by reducing infant mortality. However, this relationship only holds if we reduce early mortality, and not by reducing the rate of ageing,” said Fernando Colchero.

Using statistics and mathematics, Alberts and colleagues showed that mortality rates fit a U-shaped curve throughout life. Younger individuals experience higher mortality, which evens out in the middle of life and then picks up again as we go through the process of aging. These analyses show why infant, child, and young person mortality typically lowers life expectancy throughout underdeveloped societies where infant mortality can be higher.

When the Young Survive, Life Expectancy Increases

By digging deeper into the primate lifespan data, Alberts and colleagues showed that life expectancy increases when lifespan equality does, too. The optimal way to increase lifespan would be for most of the population to live somewhere near the maximum lifespan, which happens in many developed societies. The catch is that once infant and juvenile mortality are low, we need to develop a new means to slow the aging rate to increase life expectancy.

(Colchero et al., 2021 | Nature Communications) As infants and juveniles live longer, there is less variance in people’s lifespans, and overall life expectancy increases. Lifespan equality increases when more people live to similar ages. When lifespan equality improves in females (a) and males (b), so does overall life expectancy. Throughout primate species, death rates during life happen in a U-shaped curve, where infant and juvenile mortality is higher than in middle-aged years. Then, as aging progresses, adult death rates climb again (c). These analyses account for why higher infant and juvenile mortality can counteract achieving lifespan equality in underdeveloped societies.

Will Anti-Aging Therapeutics Increase Life Expectancy? 

“Not all is lost,” said Fernando Colchero, a lead author on the study, in a press release. “Medical science has advanced at an unprecedented pace, so maybe science might succeed in achieving what evolution could not: to reduce the rate of ageing.”

One way to reduce the rate of aging could be targeting aging directly by boosting levels of nicotinamide adenine dinucleotide (NAD+) — a crucial molecule involved in over 400 metabolic reactions. NAD+ levels decline with age and are linked to age-related diseases like cardiovascular complications, neurodegenerative disorders, and metabolic syndromes. Not only that, but studies have already shown that boosting NAD+ levels improves insulin sensitivity and muscle performance in humans. So, increasing NAD+ levels by taking its direct precursor nicotinamide mononucleotide (NMN) could offer a way to reduce the aging rate.

As more people start using therapeutics to target aging directly, breaking through the cap on maximum lifespan may become possible. Even using already available breakthroughs that reduce the aging rate like NMN may extend life expectancy once more people adopt its use. We’ll have to wait to see how much we can extend our life expectancy with these new therapeutic technologies.