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キーワード:
Aging; cancer, cardiovascular disease, dementia, DNA methylation, epigenetics, glucocorticoid signaling, stress
要旨:
Life stress has been associated with accelerated cellular aging and
increased risk for developing aging related diseases; however, the
underlying molecular mechanisms remain elusive. A highly relevant
process that may underlie this association is epigenetic regulation. In
this review, we build upon existing evidence to propose a model whereby
exposure to life stress, in part via its effects on the hypothalamic
pituitary axis and the glucocorticoid signaling system, may alter the
epigenetic landscape across the lifespan and, consequently, influence
genomic regulation and function in ways that are conducive to the
development of aging-related diseases. This model is supported by recent
studies showing that life stressors and stress-related phenotypes can
accelerate epigenetic aging, a measure that is based on DNA methylation
prediction of chronological age and has been associated with several
aging-related disease phenotypes. We discuss the implications of this
model for the prevention and treatment of aging-related diseases, as
well as the challenges and limitations of this line of research. (C)
2016 Elsevier Ltd. All rights reserved.
