| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
* Medical Scientist Training Program, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA; and
Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA
1Correspondence: Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, 1656 Linden Dr., Madison, WI 53706, USA. E-mail: jma{at}ahabs.wisc.edu
The in vivo cellular impact of age-associated mitochondrial DNA mutations is unknown. We hypothesized that mitochondrial DNA deletion mutations contribute to the fiber atrophy and loss that cause sarcopenia, the age-related decline of muscle mass and function. We examined 82,713 rectus femoris muscle fibers from Fischer 344 x Brown Norway F1 hybrid rats of ages 5, 18, and 38 months through 1000 microns by serial cryosectioning and histochemical staining for cytochrome c oxidase and succinate dehydrogenase. Between 5 and 38 months of age, the rectus femoris muscle in the hybrid rat demonstrated a 33% decrease in mass concomitant with a 30% decrease in total fibers at the muscle mid-belly. We observed significant increases in the number of mitochondrial abnormalities with age from 289 ± 8 ETS abnormal fibers in the entire 5-month-old rectus femoris to 1094 ± 126 in the 38-month-old as calculated from the volume density of these abnormalities. Segmental mitochondrial abnormalities contained mitochondrial DNA deletion mutations as revealed by laser capture microdissection and whole mitochondrial genome amplification. Muscle fibers harboring mitochondrial deletions often displayed atrophy, splitting and increased steady-state levels of oxidative nucleic damage. These data suggest a causal role for age-associated mitochondrial DNA deletion mutations in sarcopenia.—Wanagat, J., Cao, Z., Pathare, P., Aiken, J. M. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia.
Key Words: aging • skeletal muscle • laser capture microdissection
This article has been cited by other articles:
|
|
 |
|
  H. Fukui and C. T. Moraes Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons Hum. Mol. Genet., March 15, 2009; 18(6): 1028 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Lushaj, J. K. Johnson, D. McKenzie, and J. M. Aiken Sarcopenia Accelerates at Advanced Ages in Fisher 344xBrown Norway Rats J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2008; 63(9): 921 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Krishnan, L. C. Greaves, A. K. Reeve, and D. Turnbull The ageing mitochondrial genome Nucleic Acids Res., December 3, 2007; 35(22): 7399 - 7405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Passos, G. Saretzki, and T. von Zglinicki DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res., December 3, 2007; 35(22): 7505 - 7513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. McKiernan, V. C. Tuen, K. Baldwin, J. Wanagat, A. Djamali, and J. M. Aiken Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1751 - F1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Herbst, J. W. Pak, D. McKenzie, E. Bua, M. Bassiouni, and J. M. Aiken Accumulation of Mitochondrial DNA Deletion Mutations in Aged Muscle Fibers: Evidence for a Causal Role in Muscle Fiber Loss J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2007; 62(3): 235 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zangarelli, E. Chanseaume, B. Morio, C. Brugere, L. Mosoni, P. Rousset, C. Giraudet, V. Patrac, P. Gachon, Y. Boirie, et al. Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21-month-old rats: a mitochondria-mediated pathway FASEB J, December 1, 2006; 20(14): 2439 - 2450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Kujoth, C. Leeuwenburgh, and T. A. Prolla Mitochondrial DNA mutations and apoptosis in Mammalian aging. Cancer Res., August 1, 2006; 66(15): 7386 - 7389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Baker, A. C. Betik, D. J. Krause, and R. T. Hepple No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity. J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2006; 61(7): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Anderson and P. D. Neufer Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation Am J Physiol Cell Physiol, March 1, 2006; 290(3): C844 - C851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. McMullen and F. H. Andrade Contractile dysfunction and altered metabolic profile of the aging rat thyroarytenoid muscle J Appl Physiol, February 1, 2006; 100(2): 602 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Hacker, S. H. McKiernan, P. S. Douglas, J. Wanagat, and J. M. Aiken Age-related changes in cardiac structure and function in Fischer 344 x Brown Norway hybrid rats Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H304 - H311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Kujoth, A. Hiona, T. D. Pugh, S. Someya, K. Panzer, S. E. Wohlgemuth, T. Hofer, A. Y. Seo, R. Sullivan, W. A. Jobling, et al. Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging Science, July 15, 2005; 309(5733): 481 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Pesce, A. Cormio, F. Fracasso, A. M. S. Lezza, P. Cantatore, and M. N. Gadaleta Age-Related Changes of Mitochondrial DNA Content and Mitochondrial Genotypic and Phenotypic Alterations in Rat Hind-Limb Skeletal Muscles J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(6): 715 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Hagen, D. J. Krause, D. J. Baker, M. H. Fu, M. A. Tarnopolsky, and R. T. Hepple Skeletal Muscle Aging in F344BN F1-Hybrid Rats: I. Mitochondrial Dysfunction Contributes to the Age-Associated Reduction in VO2max J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2004; 59(11): 1099 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Olfert, J. Balouch, and O. Mathieu-Costello Oxygen Consumption During Maximal Exercise in Fischer 344 x Brown Norway F1 Hybrid Rats J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2004; 59(8): B801 - B808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Hepple, K. D. Ross, and A. B. Rempfer Fiber Atrophy and Hypertrophy in Skeletal Muscles of Late Middle-Aged Fischer 344 x Brown Norway F1-Hybrid Rats J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2004; 59(2): B108 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Payne, S. L. Dodd, and C. Leeuwenburgh Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space J Appl Physiol, December 1, 2003; 95(6): 2554 - 2562. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. T. Hepple Sarcopenia--A Critical Perspective Sci. Aging Knowl. Environ., November 19, 2003; 2003(46): pe31 - 31. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Drew, S. Phaneuf, A. Dirks, C. Selman, R. Gredilla, A. Lezza, G. Barja, and C. Leeuwenburgh Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R474 - R480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Morley, H. M. Perry III, and D. K. Miller Editorial: Something About Frailty J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2002; 57(11): M698 - 704. [Full Text] [PDF]
|
|
|
|
|
|
E. A. Bua, S. H. McKiernan, J. Wanagat, D. McKenzie, and J. M. Aiken Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia J Appl Physiol, June 1, 2002; 92(6): 2617 - 2624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Droge Free Radicals in the Physiological Control of Cell Function Physiol Rev, January 1, 2002; 82(1): 47 - 95. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
