Multi-omic and biological factors associated with lifespan and healthspan across NHP clades

NIH RePORTER · NIH · R01 · $418,364 · view on reporter.nih.gov ↗

Abstract

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging and develop new biochemical and omic methods to describe biological age consistently across NHPs used in biomedical research. Without accurate measures of chronological and biological aging, it is impossible to make inferences into genetic, demographic, or physiological variables driving differences in NHP lifespan. The Nonhuman Primate Lifespan Project (NPLP) now includes data on >110,000 individual NHPs from 59 species across 15 research institutions that will be leveraged to identify demographic, clinical, and molecular biomarkers of aging and lifespan. The first aim of this proposal will generate the most accurate and comprehensive characterization of sex-specific lifespan and age-at-death distributions to date for 11 biomedically-relevant species, including chimpanzees, baboons, vervets, four species of macaques, marmosets, tamarins, titi monkeys, and squirrel monkeys. It will test the influence of energetic trade-offs including body size, age at reproductive maturity, and number of offspring (in females) on lifespan across species. Aim 2 will identify shared and species-specific patterns of biological aging across 15,000 NHP lifespans based on a deficit accumulation index (DAI) generated from clinical blood chemistries collected annually to test if longer lifespans within and between species are associated with increased physiological disruption later in life and a slower pace of biological aging as characterized by a lower trajectory of deficit accumulation. This aim will focus on the most used species for translational human aging studies: baboons, vervets, rhesus macaques, and marmosets. With the lifespan and healthspan data generated in the first two aims, animals will be selected showing contrasting patterns of pace of biological aging and lifespan. Aim 3 will identify omic biomarkers that differentiate exceptionally long-lived animals to characterize pathways mediating health and lifespan differences within and between species. This will leverage existing sequence data in 2700 pedigreed NHPs to identify rare and common genetic variants associated with lifespan, healthspan, and pace of aging within species. Evolutionary conservation of the implicated genes across 77 primate species, including humans, will identify genes selected for longevity in each clade. Finally, longitudinal untargeted plasma proteomic data will be generated in 48 animals with extreme or median longevity from each of the four species (a total of 576 plasma proteomes). This data will be used to identify the underlying biology driving differences in longevity within and between species including pace of aging as characterized in Aim 2. It is hypothesized that while individual genomic and proteomic variants driving longevity may be specific to one species or clade, when taken together, the variants will coalesce to highlight a limited number of biological pat...

Key facts

NIH application ID
10936738
Project number
1R01AG087957-01
Recipient
WAKE FOREST UNIVERSITY HEALTH SCIENCES
Principal Investigator
Ellen Elizabeth Quillen
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$418,364
Award type
1
Project period
2024-07-22 → 2029-06-30