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http://f1000biology.com/graphics/biology/f1000evaluation.gifExceptional, F1000 Factor: 10

Telomere dysfunction induces metabolic and mitochondrial compromise. Sahin E, Colla S, Liesa M, Moslehi J, Mulligan R, Shirihai OS, Chin L, DePinho RA. Nature. 2011 Feb 17; 470(7334):359-65

Evaluated by | Kevin Conley, University of Washington, United States of America

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Tying together the loose ends of aging: a common thread ties telomere deterioration to growth arrest and metabolic failure in old cells. 

Aging involves a wide range of cellular changes such as telomere shortening, growth arrest, DNA damage and mitochondrial dysfunction. A new paper by Sahin et al. summarizes work that links these loose ends into a common thread. In proliferating tissue, this thread starts with telomere shortening and runs through the growth suppressor and apoptotic regulator, p53, and ends with aging and degeneration.

The new insight for less proliferative tissues such as heart, liver and skeletal muscle is that p53 not only arrests growth but suppresses the 'master switch' activating mitochondrial function and biogenesis, peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC-1). The result is a failure to activate and support metabolism, which facilitates the physiological decline, reactive oxygen species (ROS) generation and mitochondrial dysfunction characteristic of the aging cell. Thus, telomere dysfunction not only connects via p53 to cell-growth arrest but also to downregulation of metabolism to set the stage for cell death. A promising place to halt this unraveling of the cell with age may start by preventing the fraying of the telomere to maintain cell activity and avoid the metabolic failure of a dying cell.


Evaluated 16 Mar 2011
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