title: Differential regulation of actin polymerization following activation of resting T lymphocytes from young and aged mice.
abstract: Actin polymerization accompanies receptor-mediated responses and is correlated with motility-related events. In T lymphocytes, there is a lateral redistribution of surface receptors into caps and aggregation of actin-myosin in cytoplasmic subcaps, and these are impaired in T cells from aged individuals. This study documents marked changes in age-related cytoskeletal actin filament function which may account for the reduced motility. Basal levels of filamentous actin (F-actin) are significantly higher in purified G(o) T cells from aged C57BL/6 mice, due to a preferential increase in the CD8+ subpopulation. Following activation of the resting T cells with Concanavalin A (Con A), F-actin depolymerized in cells from young mice for 2 min, followed by rapid polymerization, reaching a plateau 200% above resting levels. In cells from 15-17-month-old mice, an attenuated depolymerization phase was seen for 45 sec, followed by little polymerization. No depolymerization or polymerization phases occurred in cells from aged mice. Phorbol 12 myristate 13-acetate (PMA), which activates protein kinase C (PKC), bypassing receptor mediated signals, induced actin polymerization to 57% of the levels of that after Con A stimulation in cells from both young and old animals and partially eliminated the differences in actin filament assembly due to age. Perturbation of the cytoskeleton with cytochalasin E (CE) potentiated proliferation of Con A-stimulated T cells from aged mice but did not completely restore the deficit attributed to immunosenescence. The results show an age-related impairment of cytoskeletal functions and suggest that differences in early signal transduction events contribute to the decrements in surface receptor motility and subsequent proliferation of T lymphocytes from older individuals.
authors.affiliation: Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
authors.forename: M A
authors.initials: MA
authors.lastname: Brock
authors.forename: F
authors.initials: F
authors.lastname: Chrest
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology; D000199:Actins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000199:Actins; D003572:Cytochalasins; D011108:Polymers; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; C007215:cytochalasin E; D013755:Tetradecanoylphorbol Acetate