# Targeting Cellular Senescence to Extend Healthspan

> **NIH NIH P01** · MAYO CLINIC ROCHESTER · 2024 · $3,544,455

## Abstract

OVERALL: Targeting Cellular Senescence to Extend Healthspan – SUMMARY
 This proposal is for the renewal of P01 AG62413, Targeting Cellular Senescence to Extend Healthspan. In
the initial funding cycle, we made major conceptual and technical advances in the understanding of cellular
senescence, its mechanistic role in the aging of three distinct tissues, and its modifiability by pharmacological
intervention. The influence and impact of this highly collaborative PPG are highlighted by over 130 publications,
complementary grants, career development awards, and significant engagement in the Common Fund Cellular
Senescence Network. Moreover, several clinical trials have been initiated, consistent with the overall goal to
build a firm foundation of multidisciplinary discovery science in cellular senescence that leads to a pipeline of
therapeutic strategies that slow or prevent age-associated diseases.to drive translational geroscience forward.
 Our progress has also yielded several exciting and critical questions centered on the molecular
underpinnings of the senescence program, including the unique and overlapping roles of p16Ink4a and p21Cip1,
the role of specific senescent cell sub-types in tissue and systemic aging, and the tractability of these cell
populations by next-generation small molecules engineered to promote their elimination (senolytics) or alter their
behavior (senomorphics). We have assembled a uniquely qualified, highly collaborative, and multidisciplinary
team to pursue these new and important scientific directions in the renewal through three tissue-centered
projects and four highly complementary cores. The projects are Cellular Senescence and Bone Aging (Project
1), Cellular Senescence and Skeletal Muscle Aging (Project 2), and Cellular Senescence and Brain Aging
(Project 3). The multidisciplinary cores consist of an Administrative and Systems Biology Core (Core A), a
Common Mouse Models Core (Core B), a Drug Discovery and Development Core (Core C), and a Senescence
Molecular Phenotyping Core (Core D), each armed with innovative technologies and the appropriate expertise.
Collectively, through the coordination, integration, and analysis of research activities and results across the three
projects and four cores detailed in this application, this PPG will yield fundamental insights into the governing
roles of p16Ink4a and p21Cip1 in cellular senescence and aging, critical data on the therapeutic potential of
senotherapeutic compounds for age-related tissue dysfunction, and an advanced understanding and new
hypotheses regarding cellular senescence as a mediator of inter-organ communication between bone, skeletal
muscle, and brain.

## Key facts

- **NIH application ID:** 10845134
- **Project number:** 2P01AG062413-06
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Sundeep Khosla
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,544,455
- **Award type:** 2
- **Project period:** 2019-06-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845134

## Citation

> US National Institutes of Health, RePORTER application 10845134, Targeting Cellular Senescence to Extend Healthspan (2P01AG062413-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10845134. Licensed CC0.

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