Telomeres play an essential role in maintaining chromosomal integrity in the face of physiological stressors. Although the age-related shortening of TL (telomere length) in highly proliferative tissue is predominantly due to the replication process, the mechanism for telomere shortening in skeletal muscle, which is minimally proliferative, is unclear. By studying TL in both the upper and lower limbs of the young, old-mobile and old-immobile subjects and by virtue of the bipedal nature of human locomotion, which declines with age, it may be possible to elucidate the mechanism(s) responsible for cellular aging of skeletal muscle. With this approach, we revealed that TL (~15 kb) in arm skeletal muscle is unaffected by age. In contrast TL fell progressively in the legs across the young (~15 kb), the old mobile (~13 kb) and old immobile (~11 kb) subjects. Interestingly, there was a reciprocal increase in leg muscle free radicals across these groups that was correlated with TL (r=0.7), with no such relationship in the arm (r=0.09). Our results document that chronological age does not affect the cellular aging of skeletal muscle, but reveals that physical inactivity, probably mediated by free radicals, has a profound effect upon this process.
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June 04 2014
Cellular aging of skeletal muscle: telomeric and free radical evidence that physical inactivity is responsible and not age
Massimo Venturelli;
Massimo Venturelli
1
*Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, U.S.A.
†Mons Mazzali Foundation, Mantova, Italy
‡Department of Neurological, and Movement Sciences, University of Verona, Verona, Italy
§Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
Correspondence: Dr Massimo Venturelli (email [email protected]).
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Garrett R. Morgan;
Garrett R. Morgan
1
*Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, U.S.A.
∥Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
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Anthony J. Donato;
Anthony J. Donato
*Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, U.S.A.
∥Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
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Van Reese;
Van Reese
*Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, U.S.A.
∥Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
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Renato Bottura;
Renato Bottura
†Mons Mazzali Foundation, Mantova, Italy
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Cantor Tarperi;
Cantor Tarperi
‡Department of Neurological, and Movement Sciences, University of Verona, Verona, Italy
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Chiara Milanese;
Chiara Milanese
‡Department of Neurological, and Movement Sciences, University of Verona, Verona, Italy
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Federico Schena;
Federico Schena
‡Department of Neurological, and Movement Sciences, University of Verona, Verona, Italy
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Carlo Reggiani;
Carlo Reggiani
¶Department of Biomedical Sciences, University of Padova, Padova, Italy
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Fabio Naro;
Fabio Naro
**DAHFMO Unit of Histology and Medical Embryology, Sapienza University, Rome, Italy
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Richard M. Cawthon;
Richard M. Cawthon
††Department of Human Genetics, University of Utah, Salt Lake City, Utah, U.S.A.
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Russell S. Richardson
Russell S. Richardson
*Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, U.S.A.
∥Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, U.S.A.
‡‡Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah, U.S.A.
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Publisher: Portland Press Ltd
Received:
January 20 2014
Revision Received:
March 11 2014
Accepted:
April 08 2014
Accepted Manuscript online:
April 08 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (6): 415–421.
Article history
Received:
January 20 2014
Revision Received:
March 11 2014
Accepted:
April 08 2014
Accepted Manuscript online:
April 08 2014
Citation
Massimo Venturelli, Garrett R. Morgan, Anthony J. Donato, Van Reese, Renato Bottura, Cantor Tarperi, Chiara Milanese, Federico Schena, Carlo Reggiani, Fabio Naro, Richard M. Cawthon, Russell S. Richardson; Cellular aging of skeletal muscle: telomeric and free radical evidence that physical inactivity is responsible and not age. Clin Sci (Lond) 1 September 2014; 127 (6): 415–421. doi: https://doi.org/10.1042/CS20140051
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