Evolution of natural lifespan variation and molecular strategies of extended lifespan
- Virginia Commonwealth University, United States
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore
- University of Washington, United States
- Brigham and Women's Hospital, Harvard Medical School, United States
- Chinese Academy of Sciences, Institute of Zoology, China
- Harvard medical school, United States
- University of Houston - Clear Lake, United States
Abstract
To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan. Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in replicative lifespan across wild yeast isolates, as well as genes, metabolites and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism and mitochondrial function in long-lived strains. Overall, our multi-omic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. RNA-seq data were deposited with the NCBI Gene Expression Omnibus (GEO) with accession number GSE188294.
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Evolution of Natural Lifespan Variation and Molecular Strategies of Extended LifespanNCBI Gene Expression Omnibus, GSE188294.
Article and author information
Author details
Funding
National Institutes of Health (1K01AG060040)
- Alaattin Kaya
National Institutes of Health (AG067782)
- Vadim N Gladyshev
National Institutes of Health (AG064223)
- Vadim N Gladyshev
National Institutes of Health (AG049494)
- Daniel EL Promislow
National Institutes of Health (T32 AG052354)
- Mitchell Lee
Nathan Shock Center-University of Washington (P30AG013280)
- Alaattin Kaya
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Kaya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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