# Centenarian Consortium Project

> **NIH NIH U19** · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · 2021 · $947,394

## Abstract

With our previous Longevity Consortium (LC) support, we brought together four extreme longevity (EL) studies
that have agreed to share their individual level genetic and phenotypic data for more powerful genetic
association analyses of human EL. Working closely with the other LC projects and cores, we will utilize these
and developed unique resources to achieve 3 primary goals: (1) discover additional rare/uncommon EL and
compression of morbidity genetic variants; (2) analyze gene expression profiles associated with EL-genetic
variants to be used to search for healthy aging therapeutics; (3) strategically enroll new participants in the New
England Centenarian Study (NECS) to provide biomaterial and phenotypic and genetic data for discovery-
phase and validation/replication and follow-up experiments for this and other LC projects and cores.
Specifically, in Aim 1 (Discovery) we propose to conduct a genome-wide association mega-analysis of EL and
selected sub-phenotypes using data from 2,070 centenarians and 6,259 controls aggregated from the 4
longevity studies. The Japanese Centenarian Study, Health and Retirement Study, the Danish Longevity
Study, and new data from Aim 3 will provide independent replication. In Aim 2 (Translation) we will link genetic
data to whole blood gene expression data generated from 400 Long Life Family Study (LLFS) subjects, ages
ranging from 50 to 110 years. These data will be used to generate expression quantitative trait loci (eQTLs)
and gene/protein sets associated with significant eQTLs that are also associated with EL. Bioinformatics
analyses in conjunction with the Chemoinformatics core will be aimed at discovering biomolecules and existing
drugs that mimic the effects of the EL-associated mechanisms naturally occurring in people with EL genotypes.
Mediation analysis will be used to investigate the joint effects of EL-promoting variants and their associated
molecular signatures on age of onset of dementia, diabetes, cardiovascular disease, stroke, and cognitive
impairment. These analyses will characterize the healthy aging patterns that might be enabled by the
candidate compounds. In Aim 3 (discovery, validation and follow-up) we will identify 10-15 already enrolled
families with informative patterns of familial EL from the collaborating EL studies. We will enroll additional
critical family members from these families (e.g. siblings, cousins, etc) and use next generation whole genome
sequencing to discover novel, rare EL-variants and to perform fine mapping of variants discovered in Aim 1.
Newly enrolled subjects from these families as well as non-familial 103+ year olds will also provide data and
biomaterial for planned studies by the other LC projects and cores. Through these aims and in collaboration
with other LC projects and cores, the Centenarians Project will build on resources and findings from the
previous cycle of the LC to discover new genetic variants associated with EL, integrate genetic and molecular...

## Key facts

- **NIH application ID:** 10210340
- **Project number:** 5U19AG023122-14
- **Recipient organization:** CALIFORNIA PACIFIC MED CTR RES INSTITUTE
- **Principal Investigator:** THOMAS T PERLS
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $947,394
- **Award type:** 5
- **Project period:** 2004-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210340

## Citation

> US National Institutes of Health, RePORTER application 10210340, Centenarian Consortium Project (5U19AG023122-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210340. Licensed CC0.

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