# Cellular Aging and Rejuvenation: A Comprehensive Picture from a Dynamic and Network Perspective

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $618,220

## Abstract

Project Summary
Aging can be characterized as the progressive loss of homeostasis starting at maturity and ending with
senescence and death. Discoveries of the molecular mechanisms of aging can enable the development of new
therapies to block age-associated disease and extend healthspan, the healthy years of life. This goal has been
elusive even in the simplest model eukaryote, single-celled budding yeast. Yeast longevity has been
associated with each of hundreds of genes. Such complexity suggests that yeast aging is controlled by
interactions between many molecules and organelles, with any link in this network potentially subject to
compromise during a given cell division. But the chain of molecular events by which homeostasis is gradually
lost has been obscure to date, in part due to the reliance of the field on bulk-culture measurements in the study
of the genomics of aging. The premise of the current proposal is that dissecting the breakdown of the network
in many single cells — observing its many facets over time, perturbing them, and analyzing their response, is
critical for a molecular understanding of the phenomenon of aging. Toward this end, we propose to analyze
yeast molecular aging trajectories via comprehensive single-cell profiling of protein reporters (Aim 1), to
connect lifespan extending mutations to their downstream effectors through systematic epistasis analysis (Aim
2), and to test whether perturbing critical genes at a particular point in life (just-in-time interventions) can
decrease mortality rates early in life and/or extend lifespan (Aim 3). Together, these experiments will shed light
on the molecular events of the breakdown of homeostasis with age in yeast, identify dynamic interventions for
rejuvenation, and reveal novel aging genes and mechanisms to serve as prime candidates for testing in
metazoans.

## Key facts

- **NIH application ID:** 10171745
- **Project number:** 5R01AG058742-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** BRIAN K KENNEDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $618,220
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171745

## Citation

> US National Institutes of Health, RePORTER application 10171745, Cellular Aging and Rejuvenation: A Comprehensive Picture from a Dynamic and Network Perspective (5R01AG058742-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171745. Licensed CC0.

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