# Senescent Cell Burden in Human Aging and Obesity: Functional Consequences and Reduction by Caloric Restriction

> **NIH NIH K01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $104,062

## Abstract

Project Summary
A key aim of this proposal is to equip the candidate, Dr. Jamie Justice, with the expertise to become an
independent investigator who can advance interventions that extend healthy lifespan to randomized, controlled
trials in older persons. Specifically, cellular senescence is a biologic hallmark of aging that emerging preclinical
evidence indicates could have profound consequences on aging-related disease and function, and removal of
senescent cells results in robust improvements in healthspan in rodents. Translation of these interventions to
clinical trial has been proposed, yet health consequences of cell senescence and therapeutic potential has not
been evaluated in humans. Dr. Justice's preliminary data in a small number of older women are the first to
show that cells expressing tumor suppressor protein and senescence biomarker p16INK4a are present in
adipose tissue from older adults and related to worse physical function, but exercise and weight loss by caloric
restriction may mitigate this burden. The proposed research project represents a critical next step by
examining the effects of caloric restriction (CR) on cell senescence in a prospective randomized controlled trial
(RCT). The primary hypothesis is that a CR intervention will reduce senescent cell burden and this reduction
will be related to improvement in functional and metabolic outcomes. This will be accomplished by capitalizing
on a recent NIH-funded RCT (VEGGIE, R01DK103531) and the candidate's engaged inter-disciplinary
primary mentoring team (Drs. Nicklas, Ding, Kritchevsky, Kirkland). VEGGIE will determine the effects of CR
designed to achieve 10% weight loss vs. health education control in 200 men and women aged 40-65 years
with obesity (BMI 30-45 kg/m2), to characterize epigenetic and transcriptomic effects of CR in adipocytes and
peripheral blood monocytes and T cells, and associations with physical and metabolic function. We propose an
ancillary investigation in a subset of 90 participants (50-65 years, n=45 per grp) to determine the effects of
CR on senescent cell burden (Aim 1): a) proportion of p16INK4a expressing senescent cells
(immunohistochemistry) in subcutaneous abdominal adipose tissue; b) expression of senescence biomarkers
in isolated adipocytes and monocytes (RNAseq) and T cells (p16INK4a expression); and c) SASP biomarkers in
plasma (cytokine/chemokine panel). We will also examine cross-sectional associations of age and obesity with
cell senescence (Aim 2), and relationships between changes in senescence biomarkers and physical function
and metabolic outcomes (Aim 3). The research proposed is aligned with an approved NIA concept to
develop markers of aging-related biologic mechanisms for human studies. Additionally, it will provide essential
training for the candidate, who will establish expertise in cell senescence and translational research, and
develop competencies in leading clinical trials with biological outcomes. This approach provides...

## Key facts

- **NIH application ID:** 9903191
- **Project number:** 5K01AG059837-03
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jamie Nicole Justice
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $104,062
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903191

## Citation

> US National Institutes of Health, RePORTER application 9903191, Senescent Cell Burden in Human Aging and Obesity: Functional Consequences and Reduction by Caloric Restriction (5K01AG059837-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903191. Licensed CC0.

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