Cell signaling in aging and apoptosis.
Alterations in apoptotic potential, due to perturbations in cell signaling cascades, could underlie age-related organ-specific cellular degeneration and death. While increased apoptosis could lead to cell loss, as in neuronal degeneration, loss of apoptosis competence might well result in the loss of phenotypic fidelity of somatic cells, which could explain to some extent, the age-related increase in cancer incidence. Results from our laboratory indicate that after subjecting young and old rats to genotoxic stress in the form of methyl methanesulfonate (MMS), an apoptotic response is quickly mounted in the liver of the young animals but virtually absent in the same organ of old animals (Nature Med. 8 (2002) 3). To address the possible molecular signaling defect(s) responsible for the age-related dysfunction of apoptosis in response to MMS, mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases (ERKs), c-Jun NH(2)-terminal kinases (JNKs) and p38 MAPKs, were evaluated in the liver of young and old rats after MMS treatment. The results demonstrated distinct age-specific patterns of MMS-induced MAPKs activation, suggesting that the balance between cell survival and apoptosis after genotoxic stress may be impaired during aging. These results are discussed in terms of the relative importance in aging of biological redundancy, a concept put forward by the late Bernard Strehler, and cellular fidelity.
Suh
Yousin
Y
Departments of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, Seoul, 110-799, South Korea. suhys@plazal.snu.ac.kr
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D016922:Cellular Senescence; D015536:Down-Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009153:Mutagens; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D009153:Mutagens; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases