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.
Stated simply, the why and how of sex-specific aging are questions without unifying answers – answers that have broad implications for conservation, agriculture, and human health. Mechanistic hypotheses for variation in sex-specific aging derive from genetics (Theme 1), organismal biology (Theme 2), quantitative genetics (Theme 3), and evolutionary biology (Theme 4).
THEME 1: How do sex chromosomes and sex determining mechanisms contribute to sex-specific aging?
Naturally occurring variation in sex-determining mechanisms is abundant (e.g., genetic sex determination vs. environmental sex determination (ESD)). Theme 1 leverages variation in sex-determining mechanisms, sex chromosomes, and species in which sex-specific genome features can be manipulated, to test their role in sex-specific aging.
Specifically, we are undertaking the following projects:
1.1 How does sex determining mechanism affect sex-specific aging phenotypes?
1.2 How does sex-specific aging respond to altered heterochromatin differences between the sexes?
1.3 How do sex differences in aging phenotypes respond to manipulations of dosage compensation?
THEME 2: How does variation in physiology and morphology contribute to sex-specific aging?
Natural variation in sex-specific organismal biology is abundant – ranging from species where one sex has heightened cellular stress responses, or one sex has greater body size. Theme 2 leverages this variation and species in which sex differences can be manipulated, to test their impact on sex-specific aging phenotypes.
Specifically, we are undertaking the following projects:
2.1 How do sex, morphology, and physiology interact to impact sex-specific aging?
2.2 How does sex-specific aging respond to the induction of cellular stress responses?
2.3 Can we eliminate sex differences in aging phenotypes by experimentally evolving size monomorphism through selective breeding?
THEME 3: How does sex-by-environment plasticity contribute to sex-specific aging?
Sexes can respond differently to environmental perturbations, and can even change phenotypic sex. Theme 3 leverages long-term field studies, controlled laboratory studies, and novel sex-reversal studies to test for the contribution of phenotypic plasticity to sex-specific aging.
Specifically, we are undertaking the following projects:
3.1 Do sex-by-temperature interactions in wild populations sampled along thermal clines result in sex differences in aging phenotypes?
3.2 How do sex-by-temperature interactions in laboratory reciprocal transplant populations influence sex differences in aging phenotypes?
3.3 How does sex-reversal impact aging phenotypes, and does the mortality trajectory follow that of the genotypic sex or the phenotypic sex?
experiments under IISAGE. TSD: Temperature sex determination.
THEME 4: How repeatable, fixed, and/or labile are sex-specific mechanisms of aging across animal diversity?
Integrating across Themes 1-3, IISAGE will identify common vs. lineage-specific rules in sex-specific aging. These integrated interaction network analyses, spanning multiple disciplines and animal lineages, will distinguish between taxon-specific processes impacting sex differences in aging versus rules that apply across animal lineages.
Specifically, we are undertaking the following projects:
4.1 What are the universal mechanisms of sex-specific aging from species contrasts across a phylogeny, that correspond to gradients of sex determination and/or from the manipulations that alter sex differences in aging/lifespan?
4.2 What are the molecular pathways implicated in sex-specific aging that are conserved across species and environments?
4.3 What are the cellular and organismal factors that predict evolutionary change in sex-specific aging?
