Socioenvironmental and demographic modifiers of aging in nonhuman animals

Abstract

Across many species, chronological age is the greatest predictor of mortality and the leading risk factor for many non-communicable diseases. However, not all individuals within a species exhibit the same age-related declines in health. For example, some individuals develop early-onset of age-associated diseases while others never develop certain age-associated phenotypes. Understanding what predicts inter-individual pace of aging remains a key question in evolutionary biology and human health. It remains unknown how many intrinsic (e.g., body size) and extrinsic (e.g., environment) factors affect aging and, ultimately, health and survival. Further, aging is a complex phenotype that can vary across organ systems within an individual. Here, I investigated how several pertinent intrinsic and extrinsic variables impact age-related cognitive and immunological phenotypes in two species. First, I tested whether cognitive aging was associated with an intrinsic factor (i.e., body size) in domestic dogs, a species in which individuals have dramatically different rates of size-associated physical aging. I found that dogs from all breeds, regardless of size, showed approximately similar rates of cognitive aging, despite smaller breeds having lifespans approximately twice as long as larger breed dogs. Secondly, I tested how aging of the peripheral immune system, which can directly affect health and morbidity, was affected by an extrinsic modifier: extreme environmental adversity. Specifically, I investigated the extent to which a major hurricane affected immunological aging at the transcriptomic and epigenomic (i.e., DNA methylation) levels, in a key biomedical model organism (rhesus macaques). I found that 4% of genes and 13% of CpG sites were significantly associated with exposure to a major hurricane and that post-hurricane differential expression and methylation were associated with inflammatory processes. Further, transcriptomic age of individuals sampled after the hurricane were predicted to be an average of 2 years older than individuals sampled before the storm, hinting that the hurricane may have accelerated transcriptomic aging in this population. Together, this work uncovers novel intrinsic and extrinsic modifiers of aging at cognitive and immune levels that are highly pertinent to an organism’s health.