# EFFECT OF ADVANCED AGE ON HUMAN NAIVE AND MEMORY T CELLS

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1992 · $157,723

## Abstract

Decreased T lymphocyte functional responses are consistently found in
advanced age in humans.  Advanced age is also associated with a decrease
in antigenically "naive" or "virgin" T cells and an increase in numbers
of "memory" T cells that mediate recall responses in human peripheral
blood.  The specific focus of this project is to determine the functional
linkage between this change in peripheral blood T cell subsets and the
diminished activation responses of peripheral human T cells observed in
vitro in advanced age.  This proposal rests on the hypothesis that
persistence of memory T cells leads to increased average biological age
of these cells in old subjects, compared to young donors.  The increased
age of this subset results in T cells that become refractory to
activation stimuli leading to the decline in in vitro activation
responses, with little or no effect on the functional responses of the
"naive" T cell subset.  The Specific Aims of this proposal are: 1) To
determine the effects of advanced age on surface marker expression and
physical properties of human "naive" and "memory" T cells.  The
experimental approach for this Aim will be to characterize T cell subsets
from older subjects by determining expression of various adhesion
receptors on the cell surface, distribution of cell size, density and
RNA/DNA content, membrane microviscosity and lateral diffusion of
membrane proteins. 2) To determine the effects of advanced age on
functional responses of "naive" and "memory" T cell subsets.  Purified
populations of "naive" and "memory" T cells will be analyzed by a variety
of functional assays including proliferative responses to mitogens and
recall antigens, lymphokine secretion, receptor expression following
activation, increase of intracellular free calcium by both bulk culture
and single cell assays, and the kinetics of conversion of naive to memory
cells following activation. 3) To quantitate, isolate and characterize T
cells that become refractory to activation stimuli in advanced age.  We
will use the uptake of merocyanine dye as an early marker of activation,
expression of the IL-2 receptor, the protooncogene products c-myc and
c-myb and DNA content to quantitate the numbers of responsive and
nonresponsive cells.  These methods will allow surface marker
characterization and sorting of viable cells.  The nonresponding cells
will be examined for membrane alterations, heat shock response,
proliferative responses to PMA and ionomycin and changes in nuclear
function.  The results are expected to lead to insights not only into the
basis of depressed immune function in advanced age, but also into the
basic mechanisms of in vivo cellular aging.

## Key facts

- **NIH application ID:** 3121053
- **Project number:** 5R01AG009246-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** JAMES J O'LEARY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $157,723
- **Award type:** 5
- **Project period:** 1991-09-01 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121053

## Citation

> US National Institutes of Health, RePORTER application 3121053, EFFECT OF ADVANCED AGE ON HUMAN NAIVE AND MEMORY T CELLS (5R01AG009246-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121053. Licensed CC0.

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