# Thymic and peripheral Aspects of T cell Aging and Rejuvenation

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $322,747

## Abstract

Infectious disease, cancer, and autoimmune disorders affect hundreds of millions of older adults, reducing
length and quality of life across the globe and inflicting a massive economic burden on society. Yet, despite
decades of research, restoring protective immunity in older adults has remained elusive. One critical factor
contributing to age-related immune decline is a loss of naïve T (TN) cell numbers and function. Thus,
rejuvenation of T cell function is highly desirable in order to enhance protective immunity and overall
healthspan in older adults.
 This T cell Rejuvenation Program Project is centered on two key questions: (1) why do TN cell numbers and
function deteriorate with age and; (2) what can be done about it? The premise of the program is that TN cell
aging is multifactorial and that it can only be resolved by targeting multiple defects. Thymic involution and the
resulting decline in T cell production is an early event leading to immunosenescence. This reduction is
compounded by a decline in TN cell maintenance and function in the periphery. These deficiencies combine to
erode the ability of the older immune system to detect and eliminate infectious agents and neoplastic cells, and
to properly guard against autoimmunity. Our goal is to identify mechanistic reasons behind reduced thymic
function as well as impaired maintenance and activity of T cells in secondary lymphoid organs, such as lymph
nodes, with aging. We will then develop combined strategies to ameliorate these defects in order to improve
immune defense in the elderly. Our hypothesis is that mechanistic dissection of defects to both thymic
production AND peripheral TN cell maintenance is required to formulate and test effective interventions
for immune system rejuvenation in the elderly.
 Four integrated projects led by experts in the field, supported by four cutting-edge cores, will test this
hypothesis and achieve the following Program Goals: 1. Define mechanistic changes in thymic and secondary
lymphoid organ aging; 2. Generate the Human-Mouse Timeline by comparing the progression of thymus,
lymph node and T cell aging in mice and humans; 3. Determine the endogenous regenerative capacity of
thymic and secondary lymphoid organ stroma over the lifespan; 4. Devise and test rejuvenation strategies to
improve thymopoiesis and peripheral T cell maintenance and function, so as to enhance protective immunity.
 Over this support period, the above goals will provide a wealth of basic knowledge that will be translated to
preclinical models and, with the help of the Human-Mouse Timeline, be poised for translation to older adults.

## Key facts

- **NIH application ID:** 10241195
- **Project number:** 3P01AG052359-04S1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** JANKO Z. NIKOLICH
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $322,747
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241195

## Citation

> US National Institutes of Health, RePORTER application 10241195, Thymic and peripheral Aspects of T cell Aging and Rejuvenation (3P01AG052359-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241195. Licensed CC0.

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