Progressive Triad-Mitochondria Un-Coupling in Aging

Abstract

An impairment of the mechanisms controlling the release of calcium from internal stores (excitation-contraction (EC) coupling) has been proposed to contribute to the age-related decline of muscle performance that accompanies aging (EC un-coupling theory). EC coupling in muscle fibers occurs at specialized intracellular junctions called calcium release units, or triads, which are specifically placed at sarcomere's I-A band transition. In recent publications we have shown that: a) in human muscle, the frequency of triads decreases significantly with age (Boncompagni et al., 2006; J Gerontol 61:995); and b) in mice, triads are tethered to mitochondria placed at the I band (Boncompagni et al., 2009; MBC 20:1059). Here we have studied the frequency, sarcomeric-localization, ultrastructure, and coupling of triads/mitochondria in EDL from male WT mice using transmission electron microscopy (TEM).Preliminary results indicates that the number of triads/100μm2 of longitudinal section in aging mice (n=4, 25-35 months of age) decreases compared to the adult mice (n=5, 3-12 months of age): 92±9 vs. 79±8. In addition, the percentage of abnormally positioned triads (longitudinal and/or oblique) increases. On the other hand, the total volume of mitochondria does not change significantly with age. However, the number of mitochondria-profiles/100μm2 of longitudinal section is reduced (54±7 vs. 43±6), suggesting a remodelling/fusion of these organelles. Finally, we have assessed the positioning of mitochondria in respect to myofibrils and triads: a) the number of mitochondria at the A band (misplaced) slightly increases with age (9% vs 3%), whereas the number of triads-mitochondria couples is significantly reduced: 39±5 vs. 26±4. Our observations indicates: a) a age-related partial disarrangement and spatial re-organization of EC coupling/mitochondrial apparatuses; and b) a decreased percentage of mitochondria functionally tethered to calcium release sites. This could in part explain the decline of muscle performance associated to increasing age.