Journal article
Impaired signal transduction in mitogen activated rat splenic lymphocytes during aging
Mechanisms of ageing and development, v 113(2)
2000
PMID: 10708257
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mitogen activated protein kinases (MAPK) are activated by a wide variety of signals leading to cell proliferation and differentiation in different cell types. With aging, there is a marked decrease in proliferation of T-lymphocytes in response to a variety of mitogens. Several age-related changes in the activation of MAPK pathways in T-lymphocytes activated via the T-cell receptor (TCR) have been described in different species. This way, some TCR proximal defects in tyrosine kinase activity have been delineated. In this study, we have used rat splenic lymphocytes to measure the effect of aging on the activation of two MAP kinase families: ERK and JNK. In order to bypass the receptor-proximal age-dependent defects previously described, we used phorbol ester (PMA) and Ca
2+ ionophore (A23187) as co-mitogens. Our results demonstrate that splenic lymphocytes from old rats have a disturbance in the activation of the ERK and JNK MAPK signal transduction pathways, that are located downstream of the receptor-proximal events. At least part of the age-related defect leading to decreased ERK activity appears to be located upstream of ERK itself, since activation of MEK is also impaired. On the other hand, the observed defects in MAPK activation do result in decreased activation of downstream events, such as c-Jun phosphorylation. Thus, we conclude that aging of splenic lymphocytes results in a functional decline in signal transduction, and at least some of these defects are located downstream of the receptor-proximal events previously described by others. The impaired activity of these two MAP kinase pathways is likely to play a role in the diminished lymphoproliferation observed in old individuals.
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Details
- Title
- Impaired signal transduction in mitogen activated rat splenic lymphocytes during aging
- Creators
- Min Li - Center for Gerontological Research, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USARobin Walter - Center for Gerontological Research, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USAClaudio Torres - Center for Gerontological Research, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USAFelipe Sierra - Center for Gerontological Research, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USA
- Publication Details
- Mechanisms of ageing and development, v 113(2)
- Publisher
- Elsevier Ireland Ltd
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000085217300002
- Scopus ID
- 2-s2.0-0033957373
- Other Identifier
- 991019169111504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Geriatrics & Gerontology