The Envirome in Aging

We can divide aging into primary aging and secondary aging. Primary aging is inherent to the operation of our biochemistry, a relentless accumulation of damage that historically we could do little about, while secondary aging is driven by the environment, such as the pathogens we encounter, particulate air pollution, bad choices in diet, and a sedentary lifestyle. There is a very large gray area where primary aging meets secondary aging, and indeed it is far from settled where the line lies. The commentary here, proposing the concept of the envirome, falls into this area of inquiry.

To determine what is primary and what is secondary in aging, we would need a comprehensive model of the detailed progression of aging. I don't expect that model to be produced any time soon. Firstly, it is a truly massive undertaking that will only be completed in this century given significant technological progress over the next few decades. Secondly, the progression of aging will become a moving target in the near future era of rejuvenation therapies. Who will care about the degree to which a specific mechanism of damage results from primary or secondary aging when it can be controlled near completely through periodic repair? The impetus to fund the deep, detailed investigation of aging will fade with the control of aging.

Although variations in the rate of aging across species suggests a strong role of genetics, the heritability of lifespan observed within each species is less than 35%, indicating that the environment plays an predominant role in aging. The reliability theory of aging portrays organisms as mechanical systems that contain components with varying probabilities of failure. Complex organisms have redundancy in vital systems (perhaps better understood as the capacity to self-repair) so that every occurrence of damage does not result in death, but rather, the organism accumulates defects (due to inefficient repair) that ultimately exhaust reparative capacity.

While, in the context of this theory, the frequency and severity of damage has been thought to be determined, at least in part, by the environment, there are few, if any, conceptual models with robust explanatory power and predictive capacity to account for the influence of the environment on the rate of aging. In this regard, the concept of the envirome, analogous to the genome, could provide a useful ontological model for studying the relationship between the environmental circumstance and genetic predisposition.

Broadly, the envirome could be thought of as an integrated set of natural, social, and personal environmental domains. The natural domain of the environment consists of ecological and geographic conditions, whereas the social environment, which lies within the natural environment, includes the built environment, social networks, and culture. Lastly, the personal environment lies within the social environment and includes the factors specific to an individual. In this model, interactions of the natural and social domains of the envirome with the genome could be viewed as the major determinants of aging. Aging, in turn, could be viewed as a progressive accrual of damage or unrepairable injury that results from a mismatch between the envirome and the genome and from exposure to adverse environmental conditions such as low socioeconomic status, smoking, or air pollution.



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