# Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration

> **NIH NIH P01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $2,031,992

## Abstract

PROJECT SUMMARY/ABSTRACT
TITLE:
Dietary Restriction, GH/IGF-1 and Mechanisms of Cellular Protection and Regeneration
ABSTACT:
Age is the major risk factor for many morbidities including cancer, cardiovascular and neurodegenerative
diseases. Biogerontology research is well positioned to help prevent or at least delay these diseases by
identifying safe strategies to retard aging so that the degree and type of cellular damage does not reach the
threshold leading to disease incidence or progression. Here we propose to bring together two biogerontology
laboratories from the University of Southern California School of Gerontology and a laboratory from Harvard
University to study the molecular mechanisms linking fasting, fasting mimicking diets and protein restriction to
reduced nutrient signaling, the stress resistance signaling network, the mitochondrial peptide humanin, and in
turn, cellular protection, regeneration, and healthspan. These studies will contribute to the identification of
drugs and dietary interventions to treat as well as prevent multiple diseases by acting on the aging process and
on multi-system regeneration and rejuvenation. An important advantage of the dietary interventions being
tested is that they are periodic and therefore have the potential to match and possibly surpass the beneficial
effects of chronic calorie restriction while minimizing the burden of chronic and extreme diets, but also
minimizing adverse effects.
 This P01 application consists of 3 major projects, an Animal and Biostatistics Core, and an
Administrative Core. Our common goals are to: 1) identify and study novel periodic dietary interventions that
promote healthspan without causing adverse effects at old ages; 2) study the mechanisms of fasting mimicking
diet- and protein restriction-dependent cellular protection, regeneration and rejuvenation with focus on the
hematopoietic and nervous systems; 3) understand the link between dietary interventions, growth pathways
and humanin to test the hypothesis that this mitochondrial peptide functions as a healthspan mediator and
determine whether it can serve as a fasting/protein restriction mimetic; 4) test the hypothesis that endogenous
H2S is a key mediator of the protective effects of dietary interventions including fasting, fasting mimicking diets
and protein restriction on resistance to ischemic and genotoxic injury to organs and cells, and study the
regulation of cysteine gamma lyase-mediated endogenous H2S production by dietary restriction, growth factors
and humanin.
 The unique background of each PI and the close collaboration between them has generated and will
continue to generate new hypotheses, novel cellular and mouse models, as well as technical and conceptual
developments. These advances will undoubtedly accelerate the research progress and support the
development of clinical trials to improve human health in ways that could not be achieved by each laboratory
performing research independently.

## Key facts

- **NIH application ID:** 9856945
- **Project number:** 5P01AG055369-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Pinchas Cohen
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,031,992
- **Award type:** 5
- **Project period:** 2018-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856945

## Citation

> US National Institutes of Health, RePORTER application 9856945, Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration (5P01AG055369-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9856945. Licensed CC0.

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