# Using an in vivo multi-lifetime model to test mechanisms of aging

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $649,679

## Abstract

Project Summary
Species exhibit stereotypic lifespans, suggesting an intrinsic hardwired limit. Our preliminary data
shows that a population of mouse T cells can be iteratively boosted in vivo and passaged among
young mice for >11 years (~4 mouse lifespans). This multi-lifespan T cell population remains
functional, does not undergo unrestrained cell division, and like young memory T cells, undergoes
rapid proliferative bursts upon further antigen/mitogen stimulation. We have now generated 10
indepdent ongoing cohorts of cells, ranging from 6-66 total boosts over 1-11 years, to study
mechanisms by which functional cells can exceed their species’ lifespan while retaining cell
identity, functional and proliferative competence, accumulating perhaps 100s or even 1000s of
cell divisions, while not exhibiting signs of uncontrolled proliferation. Specific aims will reevaluate
the Hayflick Limit, assess mutational burden and the accumulation of transcriptional noise, test
whether a young host environment is responsible for maintaining everlasting functional
persistence of transferred T cells, and evaluate metabolic adaptations that may support extreme
longevity and maintenance of proliferative potential. Our long-term goal is to understand how a
population of mammalian somatic cells has adapted the capacity to maintain vitality despite multi-
lifetime chronological aging and an excessive history of proliferation, and to ultimately apply newly
learned concepts and mechanisms to extend human health span.
.

## Key facts

- **NIH application ID:** 10856475
- **Project number:** 1R01AG086353-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** DAVID MASOPUST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $649,679
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856475

## Citation

> US National Institutes of Health, RePORTER application 10856475, Using an in vivo multi-lifetime model to test mechanisms of aging (1R01AG086353-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10856475. Licensed CC0.

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