# Multi-omics biomarkers and molecular features of aging, longevity and Alzheimer's disease

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2024 · $572,073

## Abstract

SUMMARY: While mammals are characterized by dramatic differences in lifespan, from about 2 years in shrews
to more than 200 years in the bowhead whale, how Nature achieves such diversity in the rate of aging is
unknown. This also applies to diseases, including Alzheimer’s disease and Alzheimer’s disease related
dementias (ADRD), as some species are more susceptible to them than others. Projects 4 aims to uncover the
molecular basis for natural changes in longevity and develop and apply tools to quantify these differences at the
level of molecular signatures of longevity and biomarkers of aging across mammals. We recently sequenced
and analyzed the genomes of mammals differing in lifespan, described omics-based patterns that reflect their
longevity and developed quantitative biomarkers to predict the biological age of species and the effects of
longevity interventions. Our long-term goal is to employ these molecular tools to better explain aging and its
drastically different rates across species, and ultimately develop better, unbiased approaches to extend human
lifespan, healthspan and counteract ADRD. In the current phase of the PPG, we obtained exciting data that
further support our general approach to lifespan control. We generated chromosome-level assemblies of the
genomes of longest-lived rodents, described comprehensive molecular profiles across mammals, and developed
quantitative biomarkers of aging for various mammals. We propose to benefit from these developments and, in
close collaboration with Projects 1, 2 and 3 and Cores B and C, address critical questions in our understanding
of natural differences in the aging rates and ADRD across mammals. (1) Development of species-specific and
pan-mammalian biomarkers of aging. We will develop advanced tissue-specific and pan-tissue transcriptomic
clocks for the mouse, rat, naked mole rat, and pan-rodent clocks; Alzheimer’s disease and ADRD-related aging
clocks; epigenetic clocks based on long-range sequencing; and multi-omic clocks integrating the epigenome and
transcriptome. (2) Comparative multi-omics of longevity at the basal life state. We will generate induced
pluripotent stem cells for various species of mammals, carry out comparative cross-species analyses of these
cells at the level of the transcriptome, metabolome, and epigenome, develop molecular signatures of longevity
at the embryonic state; differentiate these cells to different lineages and develop cell type-specific longevity
signatures; compare mammalian embryonic longevity signatures with the signatures of adult tissues. (3)
Applications of multi-omics biomarkers to animal models of longevity and Alzheimer’s disease. We will apply
biomarker tools to various animal models developed by this Program Project, testing the effects of interventions
in mice based on our findings in long-lived species including epigenetic modifications, whale, beaver and human
SIRT6 expression, whale CIRBP, cGAS-STING and PYHIN mutations in wild type an...

## Key facts

- **NIH application ID:** 10848569
- **Project number:** 2P01AG047200-11
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Vadim N. Gladyshev
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $572,073
- **Award type:** 2
- **Project period:** 2014-05-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848569

## Citation

> US National Institutes of Health, RePORTER application 10848569, Multi-omics biomarkers and molecular features of aging, longevity and Alzheimer's disease (2P01AG047200-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848569. Licensed CC0.

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