OVERVIEW.
Why demographic aging – i.e., the onset, rate, and duration of adult mortality trajectories – often differs between males and females is not understood. Equally perplexing is how sex-specific demographic aging is underpinned by sex-specific organismal senescence – i.e., the deterioration of biochemical and physiological processes leading to declining function with advancing age.
We have established a Biology Integration Institute (BII) to determine how genome architecture, organismal biology, and phenotypic plasticity contribute to sex-specific aging and its evolution. In many species across the animal kingdom, one sex ages faster or has a longer lifespan. Sex specific aging has significant implications for conservation, agriculture, and human health. However, no unified model exists that reveals how mechanistic and evolutionary processes cause the diverse patterns of sex-specific aging seen in nature. Furthermore, current research on sex-specific aging has been siloed because researchers primarily use discipline-specific approaches without integration.
IISAGE brings together expertise from evolutionary biology, molecular genetics, genomics, physiology, and computational biology to identify the molecular mechanisms generating sex differences in aging. Working with amniotes, fish, and insects, IISAGE will define the rules that govern sex-specific aging. For each species, we are measuring a set of cellular aging phenotypes using IISAGE shared methods, and measuring mortality trajectories where possible, and analyzing data via shared deep learning pipelines that incorporate phylogeny. For a subset of species, we are manipulating sex-specific genome architecture, physiology, and sexual-size dimorphism. Phenotypic plasticity in aging phenotypes is being measured in wild populations along thermal clines or in laboratory populations in reciprocal temperature transplants and sex reversal experiments. Together, measurements from diverse species and manipulations analyzed with a unified pipeline will allow us to test contributions of sex determination (Theme 1), organismal biology (Theme 2), and phenotypic plasticity (Theme 3) to sex-specific aging phenotypes.
Integrating across themes 1-3, we will test the generalizability of these findings across evolutionary timescales, and test for repeated evolutionary patterns, constraints, and lineage specific phenotypes (Theme 4).
