Epub Nov Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Comment in Cell Stem Cell. An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness.
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Epub Nov Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Comment in Cell Stem Cell. An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes.
Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses.
Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age.
Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons, this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses.
Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.
LA SOLUCIÓN DE LOS TELÓMEROS
Telomerase in the ciliate Tetrahymena was discovered by Carol W. Greider and Elizabeth Blackburn in An image illustrating how telomerase elongates telomere ends progressively. Telomerase reverses telomere shortening.
¿Cómo influyen los telómeros en el envejecimiento o el cáncer?