# FSH - an Aging Hormone?

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $2,306,306

## Abstract

PROGRAM SUMMARY
 Obesity and osteoporosis are global public health hazards that commonly affect older individuals and
often co-exist in postmenopausal women. While a restricted armamentarium of therapies is available for
osteoporosis, the five approved agents for obesity are limited by poor efficacy and unacceptable side effects.
Hence, new approaches to treat these two chronic conditions of aging require a collaborative and rigorous
integrative program between independent, but fully interactive laboratories. This U19 builds on a firm
foundation of rigorous and transparent research, born from a longstanding collaboration between Drs. Mone
Zaidi and Clifford Rosen, the results of which were published last year (Nature, 2017, PMID: 28538730). We
identified FSH as a unique target to prevent both obesity and osteoporosis. We raised a polyclonal antibody to
Fshβ, which, by blocking its access to the Fsh receptor (Fshr), prevented high-fat-diet-induced obesity and
ovariectomy-induced osteoporosis. In addition, our Fsh antibody triggered the appearance of energy-
producing ‘beige’ adipocytes in white adipose tissue. Based on these studies and others, we now postulate
that FSH may also be a critical aging hormone. We therefore propose to undertake a comprehensive,
multipronged and interdisciplinary study of the effects of blocking Fsh signaling, either pharmacologically using
our monoclonal anti-Fsh antibodies or genetically in Fshr-/- mice, on lifespan, fat gain, bone marrow adiposity,
and skeletal health in mice. We will also study the mechanism of Fsh action on fat cells using ThermoMice
that report ‘beiging,’ AdipoChaser mice that measure de novo adipogenesis, and state-of-the-art technologies
for transcriptome, lipidome and bioenergetic profiling. To buttress our preclinical observations and, with a view
of testing our monoclonal antibodies in people, we propose an epidemiological study of older women and men
in the AGES-Reykjavik Cohort. We will examine whether serum FSH can be used as a surrogate marker for
bone loss, visceral fat gain, bone marrow adiposity, and ultimately, fracture risk. To provide necessary
resources across the four investigative sites–Icahn School of Medicine at Mount Sinai, Maine Medical Center
Research Institute, University of Texas Southwestern Medical Center and the University of California at San
Francisco–we propose three overarching multifunctional cores: a Skeletal and Metabolic Phenotyping Core, an
Antibody Production and Testing Core, and an Administrative and Biostatistics Support Core. In sum, our U19
proposal should allow us to break new ground in our understanding of two prevalent disorders of aging, in
addition to opening new avenues for therapeutic interventions for our increasing numbers of older adults.

## Key facts

- **NIH application ID:** 10112794
- **Project number:** 5U19AG060917-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** CLIFFORD JAMES ROSEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,306,306
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112794

## Citation

> US National Institutes of Health, RePORTER application 10112794, FSH - an Aging Hormone? (5U19AG060917-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112794. Licensed CC0.

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