# Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies

> **NIH NIH UH2** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $4,302,251

## Abstract

PROJECT ABSTRACT. Centenarians (ages >100 yrs) and even more-so, semi-supercentenarians (ages 105-109
yrs) and supercentenarians (110+ yrs) are outliers not only for their exceptionally long lifespans, but also for their
longer female fertility and resistance to aging-related disability and morbidities such as Alzheimer’s disease,
heart disease, stroke, diabetes and cancer. Their offspring also exhibit delayed morbidity and lower mortality
compared to their birth cohort. Among non-human species, rodents including the naked mole rat have also
gained attention for their variation in lifespan compared to other mammals with similar body mass. Proteomic
signatures associated with extreme longevity (EL) in centenarians and integrated transcriptomic and proteomic
data in NMRs suggest that integrated analyses of multiple omics data generated from these human and animal
models of slow aging and resistance to aging related diseases can inform us about biological mechanisms that
underlie these survival and health advantages and, ultimately, about potential therapeutics to prevent diseases
such as Alzheimer’s. Two specific aims parallel the UH2 and UH3 phases of this proposal. Aim 1: In the UH2
phase, the New England Centenarian Study and the Einstein Centenarian and Offspring studies will establish a
standardized phenotypic data and biological sample collection protocol for in-person visits of 700 subjects from
each study (n=1400). Detailed cognitive function testing will determine presence or absence of probable
Alzheimer’s. The phenotyping protocol will be the same as that used by the Longevity Consortium’s Centenarian
Project (n=350), so that their data can be added to this effort for a total sample of 1,750. A world-class
multidisciplinary team will plan the multi-omics data generation and analytic and translation efforts to be executed
in Aim 2. These efforts will be paralleled by comparative transcriptomic, proteomic and microbiomic studies of
non-human mammalian species of widely different life spans and by the creation of a library of EL-specific IPSCs
that will be differentiated into unlimited numbers of hepatocytes and neurons. Aim 2: In the UH3 phase, we will
generate transcriptomic, methylomics, metabolomics, proteomic and microbiomic data from centenarians and
centenarian offspring (generated from two time points in about a third of the sample). Methods for multi-omic
data integration compiled in Aim 1 will be used to discover molecular profiles that associate with EL and healthy
aging phenotypes including delay of or escape from Alzheimer’s disease. Integration with molecular profiles from
functional studies of resiliency performed with iPSC-derived neurons and hepatocytes and with molecular profiles
associated with increased lifespan from multiple species will point to mechanisms and generate candidate small
molecule and compound therapeutics. All generated data and unique biological resources, including the EL-
iPSC derived hepatocytes and n...

## Key facts

- **NIH application ID:** 10017131
- **Project number:** 5UH2AG064704-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** THOMAS T PERLS
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,302,251
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017131

## Citation

> US National Institutes of Health, RePORTER application 10017131, Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies (5UH2AG064704-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10017131. Licensed CC0.

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