Telomere dysfunction and stem cell ageing.
Ageing is characterized by a decline in organ maintenance and repair. Adult stem cells contribute to tissue repair and organ maintenance. Thus it is conceivable that ageing is partly due to a decline of stem cell function. At molecular level, ageing is associated with an accumulation of damage affecting DNA, proteins, membranes, and organelles, as well as the formation of insoluble protein aggregates. Telomere shortening represents a cell intrinsic mechanism, which contributes to the accumulation of DNA damage during cellular ageing. Telomere dysfunction in response to critical telomere shortening induces DNA damage checkpoints that lead to cell cycle arrest and/or cell death. Checkpoint responses induced by telomere dysfunction have mostly been studied in somatic cells but there are emerging data on cell intrinsic checkpoints that impair the maintenance and function of adult stem cell in response to telomere dysfunction. Moreover, telomere dysfunction induces alterations in the stem cell environment that limit the function of adult stem cells. In this review we summarize our current knowledge on the role of telomere dysfunction in adult stem cell ageing.
Ju
Zhenyu
Z
Institute of Molecular Medicine and Max-Planck-Research Group on Stem Aging, Ulm University, Ulm, Germany.
Lenhard Rudolph
K
K
Rudolph
Lenhard
L
D053687:Adult Stem Cells / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase