# Systemic rejuvenating factors and human aging phenotypes.

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $352,063

## Abstract

Recent animal studies have identified several polypeptides or proteins that can reverse or accelerate aging
phenotypes. These candidate “rejuvenating factors” include growth/differentiation factor 11 (GDF11),
growth/differentiation factor 8 (GDF8), and inhibitors of GDF11 and GDF8: GDF11 and GDF8 propeptides,
follistatin, follistatin-related protein 3, WFIKKN1, and WFIKKN2. Two other important candidates are oxytocin
and eotaxin. Although these circulating rejuvenating factors are associated with aging phenotypes in animal
models, a major unanswered question is whether these circulating proteins or polypeptides are relevant to
human aging phenotypes. These polypeptides or proteins have been difficult to study in the blood using
conventional immunoassays, since some of the peptides or proteins exist in multiple isoforms, undergo post-
translational modifications such as cleavage or terminal degradation, or have high sequence identity with each
other. In addition, circulating antagonists can inhibit the biological activity of GDF8 and GDF11. In order to
overcome these obstacles, we developed a novel multiplexed selected reaction monitoring assay using liquid
chromatography-tandem mass spectrometry that measures thirteen plasma proteins or polypeptides
representing eight important proteins in rejuvenation research. We will test the hypothesis that plasma
concentrations of these candidate rejuvenating factors are independently associated with and predict specific
aging phenotypes in older adults. Our aim is to conduct a comprehensive assessment of circulating
rejuvenating factors and their relationships to specific aging phenotypes in humans. To address this aim, we
will measure these circulating factors in participants of the Baltimore Longitudinal Study of Aging (BLSA) and
the Lifestyle Interventions and Independence for Elders (LIFE) Study. Aging phenotypes will include prevalent
and incident sarcopenia, lower extremity physical performance, mobility disability, cognition, memory, cardiac
hypertrophy, osteoporosis, insulin resistance, and anemia. By the end of the project, we should be able to
verify or refute the association of these candidate rejuvenating factors with phenotypes of human aging.
Verification of a role for rejuvenating factors in human aging phenotypes should advance risk stratification and
targeting of specific pathways in the prevention or treatment of adverse aging outcomes.

## Key facts

- **NIH application ID:** 9932864
- **Project number:** 5R01AG057723-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RICHARD D SEMBA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,063
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932864

## Citation

> US National Institutes of Health, RePORTER application 9932864, Systemic rejuvenating factors and human aging phenotypes. (5R01AG057723-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932864. Licensed CC0.

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