Myostatin Induces DNA Damage in Skeletal Muscle of Streptozotocin-induced Type 1 Diabetic Mice

Sriram, Sandhya; Subramanian, Savitha; Juvvuna, Prasanna Kumar; McFarlane, Craig; Salerno, Mônica Senna; Kambadur, Ravi; Sharma, Mridula

doi:10.1074/jbc.m113.483115

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…In murine study, it was reported that DNA damage in muscle occurs prior to muscle degeneration (Sandri et al 1995). And decreased DNA damage accumulation in myostatin knockout mice showed decreased muscle degeneration (Sriram et al 2014). Therefore, our data b Fig.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…The changed muscle lipid metabolism has its influence on glucose metabolism and could be at the starting point of muscle insulin resistance. For this, there are currently a few hypotheses [49,[54][55][56][57][58], which go beyond the scope of this review.…”

Section: Pathophysiologic Mechanismsmentioning

confidence: 99%

Where frailty meets diabetes

Perkisas

Vandewoude

2016

Diabetes Metabolism Res

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Diabetes is a chronic illness that has an effect on multiple organ systems. Frailty is a state of increased vulnerability to stressors and a limited capacity to maintain homeostasis. It is a multidimensional concept and a dynamic condition that can improve or worsen over time. Frailty is either physical or psychological or a combination of these two components. Sarcopenia, which is the age-related loss of skeletal muscle mass and strength, is the main attributor to the physical form of frailty. Although the pathophysiology of diabetes is commonly focused on impaired insulin secretion, overload of gluconeogenesis and insulin resistance, newer insights broaden this etiologic horizon. Immunologic factors that create a chronic state of low-grade inflammation -'inflammaging' -have an influence on both the ageing process and diabetes. Persons with diabetes mellitus already tend to have an accelerated ageing process that places them at greater risk for developing frailty at an earlier age. The development of frailty -and sarcopenia -is multifactorial and includes nutritional, physical and hormonal elements; these elements are interlinked with those of diabetes. A lower muscle mass will lead to poorer glycaemic control through lower muscle glucose uptake. This leads to higher insulin secretion and insulin resistance, which is the stepping stone for diabetes itself.

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“…a) through binding to a sterol regulatory element present in the myostatin promoter to promote insulin resistance . In addition, myostatin transcription is upregulated in skeletal muscle of streptozotocin‐induced type 1 diabetic mice through the action of the Foxa2 transcription factor, which is activated due to reduced insulin signaling in type 1 diabetic muscle .…”

Section: Regulation Of Myostatinmentioning

confidence: 99%

Myostatin: Expanding horizons

et al. 2015

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Myostatin is a secreted growth and differentiation factor that belongs to the TGF-β superfamily. Myostatin is predominantly synthesized and expressed in skeletal muscle and thus exerts a huge impact on muscle growth and function. In keeping with its negative role in myogenesis, myostatin expression is tightly regulated at several levels including epigenetic, transcriptional, post-transcriptional, and post-translational. New revelations regarding myostatin regulation also offer mechanisms that could be exploited for developing myostatin antagonists. Increasingly, it is becoming clearer that besides its conventional role in muscle, myostatin plays a critical role in metabolism. Hence, molecular mechanisms by which myostatin regulates several key metabolic processes need to be further explored.

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Myostatin Induces DNA Damage in Skeletal Muscle of Streptozotocin-induced Type 1 Diabetic Mice

Cited by 15 publications

References 46 publications

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

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

Where frailty meets diabetes

Myostatin: Expanding horizons

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