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Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

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Abstract

Low mitochondriogenesis is critical to explain loss of muscle function in aging and in the development of frailty. The aim of this work was to explain the mechanism by which mitochondriogenesis is decreased in aging and to determine to which extent it may be prevented by exercise training. We used aged rats and compared them with peroxisome proliferator-activated receptor-γ coactivator-1α deleted mice (PGC-1α KO). PGC-1α KO mice showed a significant decrease in the mitochondriogenic pathway in muscle. In aged rats, we found a loss of exercise-induced expression of PGC-1α, nuclear respiratory factor-1 (NRF-1), and of cytochrome C. Thus muscle mitochondriogenesis, which is activated by exercise training in young animals, is not in aged or PGC-1α KO ones. Other stimuli to increase PGC-1α synthesis apart from exercise training, namely cold induction or thyroid hormone treatment, were effective in young rats but not in aged ones. To sum up, the low mitochondrial biogenesis associated with aging may be due to the lack of response of PGC-1α to different stimuli. Aged rats behave as PGC-1α KO mice. Results reported here highlight the role of PGC-1α in the loss of mitochondriogenesis associated with aging and point to this important transcriptional coactivator as a target for pharmacological interventions to prevent age-associated sarcopenia.

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Acknowledgements

This work was supported by grants SAF2008-00270, SAF2009-08334, and BFU2007-65803/BFI from the Spanish Ministry of Education and Science; PROMETEO/2010/074 from the Consellería de Educación de la Generalitat Valenciana. ISCIII2006-RED13-027 from the “Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)”, EU Funded COSTB35 and DPS2008-06968 from Spanish Ministry of Innovation and Science. This study has been cofinanced by FEDER funds from the European Union.

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Authors and Affiliations

  1. Laboratory “Movement Sport and Health Sciences”, University Rennes, Rennes, France

    Frederic Derbré & Arlette Gratas-Delamarche

  2. Department of Physiology, University of Valencia, Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain

    Mari Carmen Gomez-Cabrera, Ana Lucia Nascimento, Fabian Sanchis-Gomar, Vladimir Essau Martinez-Bello & Jose Viña

  3. Department of Physiology, University Complutense of Madrid, Madrid, Spain

    Jesus A. F. Tresguerres

  4. Department of Physical Education, University of Las Palmas de Gran Canaria, Canary Island, Spain

    Teresa Fuentes

  5. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain

    Maria Monsalve

  6. Department of Physiology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez, 15, Valencia, 46010, Spain

    Jose Viña

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  1. Frederic Derbré
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  2. Mari Carmen Gomez-Cabrera
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  7. Teresa Fuentes
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  10. Jose Viña
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Correspondence to Jose Viña.

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Frederic Derbré and Mari Carmen Gomez-Cabrera contributed equally to this work.

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Derbré, F., Gomez-Cabrera, M.C., Nascimento, A.L. et al. Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training. AGE 34, 669–679 (2012). https://doi.org/10.1007/s11357-011-9264-y

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