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

Abstract

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.

Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage

“…We stained the adult Drosophila abdominal tissue using phospho-histone 2Av (γH2Av), which binds to sites of DNA damage (Klattenhoff et al, 2007; Madigan et al, 2002). In Drosophila, as in other species, DNA damage is known to accumulate in muscle nuclei under conditions of physiological growth as well as with age (Bou Saada et al, 2017; Jeon et al, 2015). As expected, we observed robust γH2Av staining in lateral muscle nuclei in young (3-day-old) fruit flies with more than two γH2Av foci present in 71% of muscle nuclei (Fig.…”

Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila

“…DDR directs a cell to repair DNA double-strand breaks (DSBs), a major driver of intrinsic aging. γH2AX is a dependable indicator of DNA damage response [ 50 , 51 ]. To determine the activation of DDR in ECs when exposed to DNA damage, we examined the signal strength of γH2AvD, analogous to mammal γH2AX, in Myo-GFP + cells of the gut from Myo ts >GFP flies 1 h after the application of 5 Gy of γ-ray irradiation as an inducer of the DNA damage.…”

Ubiquitous overexpression of the DNA repair factor dPrp19 reduces DNA damage and extends Drosophila life span

“…During Drosophila aging increased levels of γH2Av are associated with age-dependent degeneration, for example, in tissues such as the intestine 33 and muscle. 38 …”