The Dog Aging Project is a long-term longitudinal study of aging in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. See more at Creevy et al, (2022) Nature 602:51-57
Sexual Dimorphism: A Continuous Multivariate Space
Sex is one of the classic models of canalization in evolutionary biology. In addition, sexual selection is a powerful driver of fantastic variation among the many sexually dimorphic species. An even more comprehensive picture of phenotypic variation however should consider the mutifaceted and dynamic nature of sexual dimorphism. We investigate the nature of sexual dimorphism in physiology, demography and metabolomic traits using Drosophila models of both natural genetic variation and canonical pathways of sexual differentiation.
Cellular Network Analysis
We also explore the insights that can be gained by analysis of cutting edge single-cell RNA profiling. This work includes dissecting patterns of gene coexpression across cells in developing Drososphila, using single-cell techniques to investigate neurodegenerative disease, and exploring the development of sex.
Mechanistic Biological Clocks
Many biomarkers have been shown to be associated not only with chronological age but also with functional measures of biological age. In human populations, it is difficult to show whether variation in biological age is truly predictive of life expectancy, as such research would require longitudinal studies over many years, or even decades. We use metabolome data from either humans and Drosophila to build clock models, which not only predict age at sampling, but at least in flies also predict lifespan and mortality. Unlike epigenetic clocks, which are difficult do draw mechanistic inference from, metabolome clocks offer insight into the molecules and pathways that may closely associate with the aging process. We are actively examining the cellular and organismal mechanisms behind such metabolome clocks.
Theoretical and empirical studies of life history evolution have long focused on trade-offs between reproduction and survival. Our recent work in collaboration with Scott Pletcher at the University of Michigan explores the notion that neural circuits, rather than downstream physiology, are at the heart of costs of mate choice and reproduction. The Promislow lab uses systems biology to understand the downstream consequences of these neuronal signals. Image from: Harvanek, Z., Lyu, Y., Gendron, C. et al. Perceptive costs of reproduction drive ageing and physiology in male Drosophila. Nat Ecol Evol 1, 0152 (2017)
Age-Related Cognitive Dysfunction in Dogs
As part of our efforts to understand healthy aging, we explore age-related diseases in dogs and in humans. We have recently found associations between physiological hallmarks of alzheimer’s disease in dog brains and their cognitive performance, opening the door to future investigation and interventional studies of neruodegenerative disease models in companion animals. Urfer, S.R. et al., GeroScience 43, 2379–2386 (2021). https://doi.org/10.1007/s11357-021-00422-1
Phenotypic variation is often influenced by the action of a large number of genes and genetic variants on a smaller number of metabolites or metabolic pathways. Our lab is actively developing models of phenotypic variation in which genetic variation may influence the levels of individual metabolites or the relationship between metabolites and, as a result, affect metabolic pathways that share direct connections to phenotype. Recent work on peroxide resistance in Drosophila indicates several ways in which this principle could manifest Harrison et al., 2020 BMC Genomics. We continue work to explore these patterns on evolutionary timescales.
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