Cellular activation after ligand-receptor interactions includes rapid polymerization of actin, and, in T lymphocytes, the concomitant lateral redistribution of surface receptors and of cytoskeletal actin. Cytochalasin E specifically depolymerizes filamentous actin (F-actin), and increased proliferation of resting T cells from old but not young mice. This suggested an age-related increase in F-actin which could impair lymphocyte functions. The F-actin content of resting (GO) and stimulated T lymphocytes from spleens of C57BL/6 mice was quantitated using a fluorescein-like fluorophore, Bodipy, conjugated to phallacidin which binds only to F-actin. Flow cytometric analysis showed that baseline levels of relative F-actin content were significantly increased in resting cells from aged mice (24-25 mo). Activation of Go T lymphocytes with Concanavalin A produced an immediate (within 60 sec.) increase in F-actin in cells from old mice and it returned to baseline levels within 2 min.; no further increase occurred for up to 40 min. In contrast, F-actin levels in cells from young mice (4-6 mo.) began to increase within 2 min. after activation and continued to rise for up to 50 min. These differences in F-actin content and polymerization kinetics may result in impairment of cytoskeletal functions and be related to the age-associated alterations in signal transduction in T lymphocytes from older individuals. A comprehensive review of the topic, Chronobiology and Aging, was written. This was requested by the associate editor of the Journal of the American Geriatrics Society.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Intramural Research (Z01)
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National Institute on Aging
United States
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