Fight Aging!

If interested in the evolution of aging, today's open access paper opens with a very readable tour of the history of thought on this topic, as well as the more recent debate between different classes of hypotheses that seek to explain the evolution of aging. The authors are opinionated, and the path leads to their favored theory, involving population-wide effects driven by infectious disease that do not require group selection, but it nonetheless covers a lot of ground and makes for an educational read. Theories of aging are much debated, perhaps in part because there are so many exceptions to the rule that must be explained away. The long lives and negligible senescence of naked mole-rats, the apparent physical immortality of hydra, the large variance in life span between near neighbor species in similar ecological niches, and so forth.

As things stand, the mainstream position on the evolution of aging is that it results from natural selection operating more strongly on early life features than on later life features. Systems and mechanisms are selected for their ability to improve early reproductive success, regardless of whether or not they fall apart later in life. Aging is inevitable, but only a side-effect of the dominance of early reproductive success as a strategy. Alternatively, and as the authors note, it is possible that aging provides some sort of benefit in evolutionary competition, and is thus under direct selection. The range of possible benefits are subtle and may only take effect over very long periods of time, however, making it hard to mount a compelling argument based on evidence rather than modeling. This is a field unlikely to come to complete consensus in the near future.

Is Aging an Inevitable Characteristic of Organic Life or an Evolutionary Adaptation?

A group of adaptive hypotheses claims that aging evolved to control epidemics of infectious diseases. Indeed, pathogens are a universal and powerful selective factor, and the intrinsic disease-independent mortality (lifespan setpoint) of the host is an important parameter in epidemiological models. If the probability of an individual becoming infected is equivalent across the lifespan and no recovery is presumed, older individuals are expected to be infected more often than younger ones. So, the removal of older individuals by aging obviously results in a decrease in chronic pathogen load. If one assumes that infection adversely affects reproduction, shortening the lifespan might paradoxically result in an increase in the population growth rate.

Disease-mediated selection of a shorter lifespan was also suggested as a hybrid model involving elements of population density control, acceleration of evolution, and disease prevention with the emphasis on overcrowding as a reason for epidemic. However, neither model is a universal explanation of aging. Both involve group selection, a condition believed to be rare in nature. Both require constant severe epidemics to sustain the selective pressure against the longer lifespan, a premise that contradicts observations. Furthermore, such epidemics should promote a fast selection of host resistance.

Using realistic epidemiological and population dynamics models, we constructed a theoretical framework, supporting the idea that pathogens may be the force behind the evolutionary benefit of aging. The new model proposes that aging can be a unifying adaptation to limit the establishment and progression of infectious diseases. First, we found that populations of short-lived individuals, in addition to reduced pathogen prevalence, bestow additional benefits when facing epidemics. Novel pathogens infecting a new host species from another species or the environment might require substantial time to adapt to a new host. Our model shows that the shorter lifespan of a species might limit the time window available for such chronic pathogens to evolve better transmissibility, thus preventing zoonotic transmissions.

Next, we found that dramatic declines in infected population densities - bottlenecks - during natural oscillations or migration into a new environment might be associated with pathogen clearance. If the last infected founders die before the density is reconstituted to levels permissive for epidemics, the pathogen will become extinct in that population. This effect depends directly on the species' lifespan. Thus, a short lifespan has population-level benefits. A simulation designed based on this hypothesis demonstrated the scenario of short lifespan selection.

Regarding the pathogen properties, the model assumes chronic pathogens with strong negative effects on reproductive fitness. Such pathogens are present in nature: evolutionary parasitology predicts pathogens to rather sterilize their hosts than shorten their lifespan to facilitate transmission. We found that pathogens with too high or too low infectivity cannot mediate selection of shorter lifespan: if a pathogen is transmitted at a very high level, it infects short-lived and long-lived populations both at high levels, producing no selectivity. If transmission is too low, the prevalence of the pathogen and, therefore, its adverse effects on long-lived strain population growth is insufficient. Selection favoring short lifespans requires a highly (90%) sterilizing pathogen or a combination of mildly (10-40%) sterilizing diseases that can provide a strong cumulative penalty in coinfected hosts.

We modeled a population of short-lived individuals invaded by a long-lived mutant. With this model, we observed the stabilizing selection of shorter lifespans that occurred by the following mechanism: (i) in the early stages, the pathogens and long-lived mutants are spatially separated from each other, allowing mutants to expand due to their low mortality, (ii) the pathogens spread in the area occupied by long-lived hosts and, due to the reasons described above, becomes more prevalent than in short-lived hosts, (iii) higher pathogen prevalence results in higher sterilization and lineage-specific population decline that, in combination with population pressure of short-lived populations, results in a complete displacement of the long-lived individuals.

Unlike previous models of pathogen control type, our scenario does not require group selection or ongoing severe epidemics to explain a limited lifespan setpoint. Importantly, our hypothesis also mitigates the problems associated with the evolution of the host's resistance to pathogens: selective pressure towards the shorter lifespan might be provided by zoonotic pathogens, the exposure to these pathogens is limited, and the likelihood for the evolution of resistance is reduced. In another scenario involving several milder pathogens, each of these pathogens confers only a little selective power to drive the evolution of resistance.