# From in vivo to in vitro heterochronic parabiosis to identify geronic factors

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $465,623

## Abstract

PROJECT SUMMARY
Exciting results from the heterochronic parabiosis model suggest the presence of rejuvenation factors in the
circulation that restore youthful characteristics to aged cells and tissues. Identification of robust anti-geronic
factors that mediate rejuvenation effects is a key to translating the potential of heterochronic parabiosis into
clinical applications. Comparative un-biased proteomic analyses followed by western blot validation of serum
samples led us to identify candidate “conserved” anti-geronic factors that decline with age in mice and humans,
including PEDF (SERPINF1) which is known to play a critical role in stem cell self-renewal, maintenance and
survival in mice. The overall goal of the proposed project is to identify and validate circulating anti-geronic factors
among our top conserved candidate factors by utilizing both in vivo and in vitro heterochronic parabiosis
experimental systems. This work will be organized to address the three critical research questions: 1) Do
candidate anti-geronic factors restore youthful properties to aged cells and tissues in vitro and in vivo?; 2) Do
candidate anti-geronic factors mediate the beneficial effects of heterochronic parabiosis on aged tissues and of
heterochronic transplantation on aged stem cells?; and 3) Do candidate anti-geronic factors alter age-related
cellular epigenomic profiles in vitro and in vivo? To achieve our goals: We will prioritize conserved candidate
anti-geronic factors by measuring their ability to phenocopy young serum in vitro (Aim 1); We will test for
necessity of anti-geronic factors to mediate beneficial effects of heterochronic parabiosis on aged tissues in vivo
(Aim 2); and We will address whether the candidate anti-geronic factors prioritized in Aim 1 and validated in Aim
2 act to alter age-related cellular epigenomic profiles both in vitro and in vivo as determined by genome-wide
analyses (Aim 3). Our long-term goal is to assess whether anti-geronic factors, alone or in combination, delay or
reverse the age-associated functional decline of cells and tissues, thereby revealing potential targets for
therapeutic intervention.

## Key facts

- **NIH application ID:** 10079736
- **Project number:** 7R01AG057433-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** THOMAS A. RANDO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $465,623
- **Award type:** 7
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079736

## Citation

> US National Institutes of Health, RePORTER application 10079736, From in vivo to in vitro heterochronic parabiosis to identify geronic factors (7R01AG057433-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10079736. Licensed CC0.

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