# Metabolomics of longevity

> **NIH NIH U19** · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · 2022 · $1,287,215

## Abstract

The project ‘Metabolomics of longevity’ will partner with all projects and cores within the Longevity Consortium
study. Its objective is to detail the metabolic biomarkers and biochemical mechanisms that differ betwee long-
lived species or subjects, in comparison to species or subjects with shorter lifespans. We specifically
investigate balancing nutritional energy, repair and prevention of metabolic damage, and metabolic responses
to stress. We further hypothesize that sustaining a healthy metabolism correlates with specific molecular
signatures that are acquired in other projects of the Longevity Consortium, so that metabolomics data can be
integrated into context analysis in a meaningful manner. Consistent with the overall emphasis and design of
the Longevity Consortium, we will focus on pathways relevant to control of metabolic regulatory capacity rather
than on disease-specific signatures.
According to these overarching aims, we will acquire and interpret high-quality metabolite data by using
targeted and untargeted mass spectrometry. We will identify and quantify over 800 known metabolites, in
addition of over 2,000 metabolic signals that lack structure identification. Metabolite classes will cover primary
amines, bile acids, steroids, inflammatory oxylipins, complex lipids, biogenic amines and miscellaneous
compounds, including dietary and drug exposome markers. Specifically, in aim 1, we will randomize samples
from four large human cohorts to compare baseline metabolomics markers of 683 subjects who continued to
live longer than 98% of subjects of the U.S. population, and compare these to 2,049 subjects who had a
shorter life span. We will integrate several statistical tools to compile a panel of longevity biomarkers that will
be validated by an independent cohort of 450 subjects who lived longer than 100 years. We will investigate all
data in a longitudinal manner by appropriate statistical tools to predict changes in a range of age-related
phenotypes such as grip strength and walking speed that ultimately may contribute to longevity. In aim 2 we
will analyze cells from over 100 long-lived and short-lived species to achieve mechanistic understanding of
conserved metabolic differences in cellular metabolic homeostasis. We will also compare long-lived mice
against shorter-lived wild type mice, including through lifespan-extending drugs such as rapamycin and
acarbose. In aim 3, we will combine literature-based food- and microbial metabolic markers into the analysis of
the human cohort studies as confounding factors that . may contribute to human longevity and that are not
under human genetic control. We will also contribute to efforts in the Orwoll-proteomics, the Girke-
chemoinformatics and the Price-systems cores by providing comprehensive metabolite/gene and
metabolite/protein annotations through integrating existing biochemical databases. We will supplement these
analyses by phenotypic context information for metabolite data through te...

## Key facts

- **NIH application ID:** 10448345
- **Project number:** 5U19AG023122-15
- **Recipient organization:** CALIFORNIA PACIFIC MED CTR RES INSTITUTE
- **Principal Investigator:** Oliver Fiehn
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,287,215
- **Award type:** 5
- **Project period:** 2004-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448345

## Citation

> US National Institutes of Health, RePORTER application 10448345, Metabolomics of longevity (5U19AG023122-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10448345. Licensed CC0.

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