# Network-Driven Dynamics of Replicative Aging

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $568,645

## Abstract

Project Summary
 Cellular aging is a complex biological process, associated with many diseases, such as cancer,
diabetes, and neurodegenerative diseases. New therapeutic approaches to slow aging hold promise for
reducing global healthcare burdens of chronic diseases. However, the development of these approaches
requires a deep understanding of the mechanisms of aging, which remains a challenging goal. Static
population-based studies are insufficient to reveal sophisticated molecular mechanisms that underlie the aging
process, because genetically identical cells have various intrinsic causes of aging and widely different rates of
aging. Furthermore, although many single genes have profound effects on lifespan, how they interact and
function within gene regulatory networks to regulate aging and how these interactions change dynamically
during aging remain largely unknown. To overcome these challenges, we have developed high-throughput
microfluidic technologies to track the dynamics of molecular processes throughout the replicative lifespans of
single S.cerevisiae cells. In the proposed research, these dynamic measurement technologies will be
integrated with computational modeling to systematically characterize and quantify the collective dynamic
behaviors of aging-related molecular networks. In Aim 1, we will quantitatively characterize the phenotypic
changes associated with distinct causes of cell aging and, based on these data, construct a phenomenological
model of the aging process, upon which we will build mechanistic models of the conserved Sir2 and protein
kinase A (PKA)-regulated molecular networks, both of which are deeply connected to aging. In particular, in
Aim 2, we will develop a mechanistic model of the Sir2-regulated molecular network to predict its dynamics and
regulatory roles during aging. High-throughout single-cell analysis will be performed to track the dynamics of
Sir2-regulated genes and test the model predictions. In Aim 3, we will systematically characterize the PKA-
regulated stress response during aging and develop a mechanistic model to quantify and predict the effects of
environmental cues on aging. We will systematically examine the dynamics and contribution of stress response
genes under various environmental perturbations. These experimental measurements will be used to test the
predictions, refine the model, and more importantly, provide insight into the basic mechanisms underlying the
environmental control of aging. To accomplish these aims, we have assembled a strong interdisciplinary team
of investigators with complementary expertise, who will work synergistically to tackle fundamental questions in
the biology of aging from a systems biology perspective.
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## Key facts

- **NIH application ID:** 9967937
- **Project number:** 5R01AG056440-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JEFF M HASTY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $568,645
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967937

## Citation

> US National Institutes of Health, RePORTER application 9967937, Network-Driven Dynamics of Replicative Aging (5R01AG056440-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9967937. Licensed CC0.

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