Sardinian Population Data Provides Evidence for a Reduced Burden of Infectious Disease to Slow the Pace of Aging
Aging is defined as an increase over time in the risk of death due to intrinsic causes. By this measure, aging has slowed over the past 150 years in most populations, particularly during the transition from an era of expensive calories and high rate of infection to an era of cheap calories and widespread use of effective antibiotics. A 60-year old today is far less impacted by aging and exhibits a far lower mortality risk than was the case for a 60-year old of two centuries past. To what degree is this late life outcome the result of improved nutrition versus a reduced burden of infection?
Given the importance of inflammation in aging, and the known impact of infectious disease on immune health over the long term, the consensus is that infection over a lifetime is more important than nutrition, even if the major contributing factor is persistent infection by just a few pathogens. Researchers here support that view by analyzing historical data from the Sardinian population that transitioned the era in which antibiotics were first introduced without also greatly changing their nutritional status. The results indicate that the use of antibiotics to control infectious disease produced a slowing of aging, and the data allows some insight into details of the period of a few decades over which that slowing took hold.
In biology, the term senescence is used to indicate the progressive accumulation of molecular damage that takes place in an organism as time goes by. This results in a gradual growth in the risk of death (demographic aging). By studying the pace at which mortality accelerates, it is possible to infer the general characteristics of the senescence process and to investigate which factors accelerate or decelerate its progression. So far, three major explanations for the determinants of senescence have been proposed: the constant senescence hypothesis; the inflammaging theory; and the calorie or energy restriction theory.
According to the constant senescence hypothesis, the pace of senescence is a biological constant among humans. As a result, senescence cannot be accelerated or decelerated by exogenous factors. Instead, the inflammation theory claims that the number and intensity of immune system responses to antigenic load in a lifetime is a fundamental factor in regulating the pace of senescence. Thus, individuals who have experienced a higher exposure to antigenic load will also experience a more rapid aging process. Finally, the calorie restriction theory, which is based on a plethora of experiments on a vast range of mammals and non-mammals, explores a reduced daily calorie intake and its positive effect on aging. In particular, a reduction in daily calorie intake is thought to slow senescence.
From a theoretical point of view, the three theories can be empirically tested. This would require a comparison of the aging process in cohorts who have experienced different nutritional regimes and different disease loads. However, the coincidence of the epidemiological transition and advent of antibiotics, from infection as majority cause of death to age-related disease as majority cause of death, with the onset of the nutrition transition, from a low to a high calorie regime, makes it difficult to isolate the effects of these two contrasting forces on mortality acceleration.
The epidemiological transition in Sardinia is unusual in that it started without any substantial modification in nutritional levels. This makes Sardinia a quasi-natural experiment where we can test the constant senescence hypothesis against the inflammation theory, without the confounding effect of changes in nutritional levels. To implement the analysis, the longitudinal life tables from 80 years onwards for Sardinian cohorts born in the period 1866-1908 were reconstituted and used to estimate the Gamma-Gompertz model: this model assumes that the individual hazard function follows the Gompertz model and that frailty is Gamma-distributed. The β parameter of the Gamma-Gompertz model, the so-called rate of aging, measures the relative derivative of the force of mortality, and in this sense, it may be used to measure how fast mortality progresses with age.
The results show that the Sardinian population experienced a dramatic reduction in the rate of aging that coincides with the onset of the epidemiological transition. The reduction in the rate of aging in an epoch characterized by a rapid reduction in infectious disease burden (probably due to quinine) appears to be consistent, at least at first sight, with the inflammation theory. The very low levels of nutrition observed in Sardinia, coupled with the dramatic fall off in the disease burden in the last years of the 19th century, might help to explain why the decline in the Sardinian rate of aging has been so dramatic compared with other European regions. The explanations advanced in the literature to justify the high prevalence of male centenarians in Sardinia have emphasized the role played by genetic factors. The possibility that genetic factors played a role in the evolution of the rate of aging in Sardinia cannot be entirely ruled out then. However, the analysis presented in this paper suggests that the very low Sardinian rate of aging at the beginning of the 20th century may depend on other factors such as nutrition and disease load.