DNA damage signaling mediates the functional antagonism between replicative senescence and terminal muscle differentiation.

Autor:	Latella L; Epigenetics and Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, 00179 Rome, Italy.; Institute of Translational Pharmacology, National Research Council of Italy, 00133 Rome, Italy., Dall'Agnese A; Development, Aging, and Regeneration Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.; Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA., Boscolo FS; Development, Aging, and Regeneration Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.; Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA., Nardoni C; Institute of Translational Pharmacology, National Research Council of Italy, 00133 Rome, Italy.; Pharmaceutical Development and Services, 00196 Roma, Italy., Cosentino M; Epigenetics and Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, 00179 Rome, Italy.; Institute of Translational Pharmacology, National Research Council of Italy, 00133 Rome, Italy., Lahm A; Epigenetics and Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, 00179 Rome, Italy., Sacco A; Development, Aging, and Regeneration Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA., Puri PL; Epigenetics and Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, 00179 Rome, Italy.; Development, Aging, and Regeneration Program, Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2017 Apr 01; Vol. 31 (7), pp. 648-659.
DOI:	10.1101/gad.293266.116
Abstrakt:	The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that, in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated activation of the myogenic program. A DDR-resistant MYOD mutant could overcome this barrier by resuming cell cycle progression. Likewise, DDR inhibition could also restore MYOD's ability to activate the myogenic program in human senescent fibroblasts. Of note, we found that cell cycle progression is necessary for the DDR-resistant MYOD mutant to reverse senescence-mediated inhibition of the myogenic program. These data provide the first evidence of DDR-mediated functional antagonism between senescence and MYOD-activated gene expression and indicate a previously unrecognized requirement of cell cycle progression for the activation of the myogenic program. (© 2017 Latella et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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