# Role of exercise-induced blood factors in rejuvenating the aged brain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $403,334

## Abstract

PROJECT SUMMARY/ABSTRACT
Aging drives regenerative and cognitive impairments in the adult brain increasing susceptibility to dementia-
related neurodegenerative diseases, such as Alzheimer's disease, in healthy individuals. Evidence suggests
that exercise can counter age-related decline in regenerative capacity and cognition in the aged brain. The
ability to reverse brain aging through systemic interventions such as exercise could enable the mitigation of
vulnerability to age-related neurodegenerative diseases, fulfilling an unmet need that is growing more pressing
as the human population ages. Despite the evident benefit of exercise, its application is hindered in the elderly
by technical barriers, with evidence that perception of physical frailty or poor health alone can decrease
adherence. Therefore, it is critical to identify accessible therapeutic approaches that confer benefits of exercise
while circumventing pre-existing limitations. We and others have previously shown that systemic
manipulations, including heterochronic parabiosis (in which the circulatory system of a young and old animal
are joined) and young blood plasma administration, likewise enhance adult neurogenesis and cognition in aged
mice1,3,13. The rejuvenating effects observed with exercise mirror those of a youthful circulation, raising the
possibility that exercise similarly functions through blood factors to exert its beneficial effects. Indeed,
preliminary data from our lab demonstrate that systemic administration of blood plasma derived from exercised
mice reverses age-related impairments in adult neurogenesis and cognition in aged mice. The purpose of the
proposed study is thus to investigate the rejuvenating and therapeutic effects of exercise-induced blood factors
on the aged brain. Specifically, our hypothesis is that systemic exposure to exercise-induced blood factors
elicits long lasting rejuvenation of regenerative and cognitive functions, while ameliorating neurodegenerative
phenotypes. We will test this theory with Three Specific Aims: 1: Characterize the kinetics of brain rejuvenation
following systemic exposure to exercise-induced blood factors. 2: Investigate the role of the exercise-induced
blood factor Gpld1 in rejuvenating the aged brain. 3: Determine the therapeutic potential of exercise-induced
blood factors in a mouse model of Alzheimer's disease. Successful completion of these studies will have
significant translational potential, identifying molecular and cellular pathways that could be targeted for novel
therapies to ameliorate dementia-related neurodegenerative diseases such as Alzheimer's disease.

## Key facts

- **NIH application ID:** 9997377
- **Project number:** 1R01AG067740-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SAUL A VILLEDA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,334
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997377

## Citation

> US National Institutes of Health, RePORTER application 9997377, Role of exercise-induced blood factors in rejuvenating the aged brain (1R01AG067740-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997377. Licensed CC0.

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