Aging affects all organisms by impairing cellular functions and causing tissue dysfunction. In skeletal muscle, impaired mass and force generation are often found in aging, and hence elderlies with weaker muscles are prone to falls and get injured. The underlying mechanisms of how aging affects muscle functions remain poorly understood and warrant further study. Skeletal muscle is one of few tissues, that possess a vast regenerative capacity, due to the presence of adult muscle stem cells, also known as satellite cells (SCs). Hence, we hypothesise that aging affects SC functions and therefore, in this study we studied whether the functions of old SCs could be improved. While SCs activate rapidly upon receiving external stimuli, conventional cell isolation approaches inducing stress to c...[ Read more ]

Aging affects all organisms by impairing cellular functions and causing tissue dysfunction. In skeletal muscle, impaired mass and force generation are often found in aging, and hence elderlies with weaker muscles are prone to falls and get injured. The underlying mechanisms of how aging affects muscle functions remain poorly understood and warrant further study. Skeletal muscle is one of few tissues, that possess a vast regenerative capacity, due to the presence of adult muscle stem cells, also known as satellite cells (SCs). Hence, we hypothesise that aging affects SC functions and therefore, in this study we studied whether the functions of old SCs could be improved. While SCs activate rapidly upon receiving external stimuli, conventional cell isolation approaches inducing stress to cells fail to capture SCs quiescence. To capture the quiescence signatures of SCs, our group developed an in situ cell fixation protocol. Using the well-established heterochronic parabiosis (HP) approach, which involves blood exchange between a young mouse and an old mouse, we aimed to rejuvenate old SCs by supplying blood factors from young mice. Together, we used heterochronic parabiosis along with our in situ cell fixation approach to study the bona fide quiescence transcriptomes of aged SCs. We found that old SCs exposed to blood from a young partner showed signs of rejuvenation while young SCs exposed to old blood experienced accelerated aging. In addition, we found the rejuvenated SCs may reside in deeper quiescence supported by upregulated quiescence-related gene expression and Notch pathways. Interestingly, the Rho GTPase effectors pathway was also upregulated in the rejuvenated SCs. Recent studies have suggested the roles of Rho GTPase in SCs quiescence; however, whether it contributes to the deepened quiescence in the rejuvenated SCs requires further study. We also observed rejuvenated SCs showing upregulation of cell death-related genes in agreement with the decline in apoptosis during aging. In summary, we observed key changes in the transcriptomes of old quiescent SCs following its apparent rejuvenation by heterochronic parabiosis. These preliminary findings suggest young blood may contain rejuvenating factors and/or old blood may contain aging factors, which should be studied further for the development of rejuvenation therapies to treat aging-related conditions.