TY - JOUR
T1 - Cell signaling in aging and apoptosis
AU - Suh, Yousin
N1 - Funding Information:
This work was supported by a research grant to Y. Suh (KRF-99-015-DP0287) from Korea Research Foundation. I thank Drs Sang Chul Park and Jan Vijg for support, critically reading the manuscript, and helpful discussions, Kang-Ae Lee for technical assistance, and Bok-Ghee Han for providing animals.
PY - 2002/4/30
Y1 - 2002/4/30
N2 - 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 NH2-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.
AB - 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 NH2-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.
KW - Aging
KW - Alkylating agents
KW - Apoptosis
KW - Cancer
KW - DNA damage
KW - Mitogen-activated protein kinase (MAPK)
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U2 - 10.1016/S0047-6374(02)00025-8
DO - 10.1016/S0047-6374(02)00025-8
M3 - Article
C2 - 12044936
AN - SCOPUS:0037198061
SN - 0047-6374
VL - 123
SP - 881
EP - 890
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 8
ER -