Age-related change in γH2AX of Drosophila muscle: its significance as a marker for muscle damage and longevity.

Muscle aging is closely related to unhealthy late-life and organismal aging. Recently, the state of differentiated cells was shown to be critical to tissue homeostasis. Thus, understanding how fully differentiated muscle cells age is required for ensuring healthy aging. Adult Drosophila muscle is a useful model for exploring the aging process of fully differentiated cells. In this study, we investigated age-related changes of γH2AX, an indicator of DNA strand breaks, in adult Drosophila muscle to document whether its changes are correlated with muscle degeneration and lifespan. The results demonstrate that γH2AX accumulation increases in adult Drosophila thoracic and leg muscles with age. Analyses of short-, normal-, and long-lived strains indicate that the age-related increase of γH2AX is closely associated with the extent of muscle degeneration, cleaved caspase-3 and poly-ubiquitin aggregates, and longevity. Further analysis of muscle-specific knockdown of heterochromatin protein 1a revealed that the excessive γH2AX accumulation in thoracic and leg muscles induces accelerated degeneration and decreases longevity. These data suggest a strong correlation between age-related muscle damage and lifespan in Drosophila. Our findings indicate that γH2AX may be a reliable biomarker for assessing muscle aging in Drosophila.