The tumor suppressor p53: cancer and aging.
Aging, like many other biological processes, is subject to regulation by genes that reside in pathways that have been conserved during evolution. The insulin/ IGF-1 pathway, mTOR pathway and p53 pathway are among those conserved pathways that impact upon longevity and aging-related diseases such as cancer. Most cancers arise in the last quarter of life span with the frequency increasing exponentially with time, and mutation accumulation in critical genes (e.g., p53) in individual cells over a lifetime is thought to be the reason. Recently, we found that the efficiency of the p53 response to stress declines significantly with age in mice, and the time of onset of this decreased p53 response correlates with the life span of mice. Given the crucial role of the p53 in tumor prevention, this decline in p53 activity at older ages in animals could contribute to the observed dramatic increases in cancer frequency, and provides a plausible explanation for the correlation between tumorigenesis and aging in addition to the accumulation of DNA mutations over lifetime. We discuss here the coordination and communication between the p53 pathway and the IGF-1-mTOR pathways, and their possible impact on cancer and longevity.
Feng
Zhaohui
Z
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.
Hu
Wenwei
W
Rajagopal
Gunaretnam
G
Levine
Arnold J
AJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases