# Diverse effects of somatopause and aging on the skeleton

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2021 · $450,746

## Abstract

ABSTRACT:
To date age-related changes in bone are thought to result from two distinct and
potentially synergistic causes: i) systemic hormonal changes, particularly somatopause,
the age-related declines in growth hormone [GH] and its mediator insulin-like growth
factor-1 [IGF-1] and ii) “intrinsic” cumulative or temporal changes in bone cell activity and
tissue properties. These processes are concomitant and overlapping, and their distinct
effects on age-related bone loss were not established. We have developed an
integrative molecular-to whole bone approach to study novel mechanisms controlling
bone integrity during aging. We build on a long-standing collaboration between Dr.
Schaffler, an expert in osteocytes and bone biomechanics, and Dr. Yakar, an expert in
GH/IGF-1 physiology, and a new collaboration with Dr. Pavlov, an expert in
mitochondria. We focus on osteocytes, which comprise > 95% of bone cells and are
extremely long-lived. Osteocytes integrate the bone's hormonal and mechanical
environment, produce the key signals that turn on osteoblasts and osteoclasts, and also
directly influence bone material properties. In this proposal we will study the effects of
the somatotropic axis on the viability and function of the aging osteocytes via the
following aims: 1) Determine the cellular mechanisms by which GH/IGF-1 affect
bone tissue quality; 2) Determine how GH/IGF-1 axis controls osteocyte viability
and metabolic flexibility during aging. Our studies link three hallmarks of aging
“altered intercellular communication”, which is central to tissue integrity, “mitochondrial
dysfunction”, which is central to cell survival, and “deregulated nutrient sensing”, which is
central to cellular metabolism. We expect unraveling the distinct and overlapping effects
of normal aging and somatopause specifically on bone health. Completion of our studies
will determine the morphological and the molecular mechanisms by which the GH/IGF-1
axis affects osteocytes of the aging skeleton.

## Key facts

- **NIH application ID:** 10144349
- **Project number:** 5R01AG056397-04
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** MITCHELL B SCHAFFLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $450,746
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144349

## Citation

> US National Institutes of Health, RePORTER application 10144349, Diverse effects of somatopause and aging on the skeleton (5R01AG056397-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144349. Licensed CC0.

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