UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans

Aging is commonly defined as the loss of global homeostasis, which results from progressive alteration of all organs function. This model is currently challenged by recent data showing that interventions that extend lifespan do not always increase the overall fitness of the organism. These data suggest the existence of tissue-specific factors that regulate the pace of aging in a cell-autonomous manner. Here, we investigated aging of Caenorhabditis elegans striated muscles at the subcellular and the physiological level. Our data show that muscle aging is characterized by a dramatic decrease in the expression of genes encoding proteins required for muscle contraction, followed by a change in mitochondria morphology, and an increase in autophagosome number. Myofilaments, however, remain unaffected during aging. We demonstrated that the conserved transcription factor UNC-120/SRF regulates muscle aging biomarkers. Interestingly, the role of UNC-120/SRF in the control of muscle aging can be dissociated from its broader effect on lifespan. In daf-2/insulin/IGF1 receptor mutants, which exhibit a delayed appearance of muscle aging biomarkers and are long-lived, disruption of unc-120 accelerates muscle aging but does not suppress the lifespan phenotype of daf-2 mutant. Conversely, unc-120 overexpression delays muscle aging but does not increase lifespan. Overall, we demonstrate that UNC-120/SRF controls the pace of muscle aging in a cell-autonomous manner downstream of the insulin/IGF1 receptor.