Linking functional decline of telomeres, mitochondria and stem cells during ageing

E Sahin, RA DePinho - nature, 2010 - nature.com
nature, 2010nature.com
The study of human genetic disorders and mutant mouse models has provided evidence
that genome maintenance mechanisms, DNA damage signalling and metabolic regulation
cooperate to drive the ageing process. In particular, age-associated telomere damage,
diminution of telomere'capping'function and associated p53 activation have emerged as
prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction
that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a …
Abstract
The study of human genetic disorders and mutant mouse models has provided evidence that genome maintenance mechanisms, DNA damage signalling and metabolic regulation cooperate to drive the ageing process. In particular, age-associated telomere damage, diminution of telomere 'capping' function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, 'stemness' and metabolism provides a framework for how diverse factors contribute to ageing and age-related disorders.
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