Fight Aging!

Today's open access paper offers one of a number of different perspectives on the present consensus regarding the causes of individual variance in life expectancy, of differences in species life span, and of changes in human life expectancy over time. Human life expectancy has increased greatly in the modern era, but this is largely due to improved control over infectious disease and other environmental factors that can cause early mortality and long-term health risks. Similarly, individual variance in life span near entirely arises from lifestyle choice and environmental factors. There is a component arising from slowed aging, but this has been an incidental side-effect of improved technologies, medical and otherwise.

The authors of the paper here suggest that life expectancy and mortality data shows that further improvements in the known environmental factors that impact health are unlikely to yield meaningful gains in human life expectancy. The lion's share of possible gains are already claimed, thanks to control of infectious disease and other outcomes of modern technologies. New approaches to age-related degeneration are needed, development programs and therapies that deliberately target the causative mechanisms of aging. Historical data says little about what human life expectancy will look like in the era of widespread use of senolytic treatments and other rejuvenation therapies now under development.

The long lives of primates and the 'invariant rate of ageing' hypothesis

The maximum human life expectancy has increased since the mid-1800s by ~3 months per year. These gains have resulted from shifting the majority of deaths from early to later and later ages, with no evidence of slowing the rate at which mortality increases with age (i.e. the 'rate of ageing'). Further substantial extensions of human longevity will depend on whether it is possible to slow the rate of ageing or otherwise reduce late life mortality. Consequently, the nature of biological constraints on ageing is a central problem in the health sciences and, because of its implications for demographic patterns, is also of long-standing interest in ecology and evolutionary biology.

Across species, rates of ageing are strongly correlated with other aspects of the life history-pre-adult mortality, age at first reproduction, birth rate, metabolic rate and generation time - as well as with morphological traits such as body size and growth rate. These correlations suggest that ageing evolves in concert with a suite of other traits, which may produce constraints on the rate of ageing within species. Indeed, researchers have long hypothesised that the rate of ageing is relatively fixed within species, not only in humans but also other animals.

This 'invariant rate of ageing' hypothesis has received mixed support. Understanding the nature and extent of biological constraints on the rate of ageing and other aspects of age-specific mortality patterns is critical for identifying possible targets of intervention to extend human lifespans, and for understanding the evolutionary forces that have shaped lifespans within and across species. Although no consensus has been reached about the invariant rate of ageing hypothesis, further evidence that biological constraints may shape human ageing comes from the remarkably consistent relationship between life expectancy at birth and lifespan equality in a diverse set of human populations. While life expectancy at birth (a measure of the 'pace' of mortality) describes the average lifespan in a population, lifespan equality (a measure of the 'shape' of mortality) describes the spread in the distribution of ages at death in a population.

To better understand biological constraints on ageing, here we answer two questions. First, is the highly regular linear relationship between life expectancy and lifespan equality in humans also evident in other primates? Second, if so, do biological constraints on ageing underlie this highly regular relationship? We first recapitulate, in nonhuman primates, the highly regular relationship between life expectancy and lifespan equality seen in humans. We next demonstrate that variation in the rate of ageing within genera is orders of magnitude smaller than variation in pre-adult and age-independent mortality. Finally, we demonstrate that changes in the rate of ageing, but not other mortality parameters, produce striking, species-atypical changes in mortality patterns. Our results support the invariant rate of ageing hypothesis, implying biological constraints on how much the human rate of ageing can be slowed.

Can we humans slow our own rate of ageing? Our findings support the idea that, in historical population when life expectancies were low, mortality improvements for infants, and in age-independent mortality, were the central contributors to the decades-long trend towards longer human life expectancies and greater lifespan equality. These improvements were largely the result of environmental influences including social, economic, and public health advances. Since the middle of the 20th century, however, declines in the baseline level of adult mortality have very likely played an increasingly important role in industrialised societies. As we show here, improvements in the environment are unlikely to translate into a substantial reduction in the rate of ageing, or in the dramatic increase in lifespan that would result from such a change. It remains to be seen if future advances in medicine can overcome the biological constraints that we have identified here, and achieve what evolution has not.