Teh Bin Tean, M.B.B.S., Ph.D. | National Cancer Centre Singapore; and Koh Hong Xiang Frederick, M.B.B.S., M.R.C.S.E, M.Med, F.R.C.S.Ed | Sengkang General Hospital
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee Year: 2020
Sarcopenia is defined as the progressive loss of muscle mass with age. One major pathophysiology of sarcopenia is the inherent loss of regenerative capacity of skeletal muscle progenitors (SMPs) which is essential for muscle fiber repair and homeostasis. However, less is known on the regulation of the regenerative capacity of aged SMPs. We hypothesized that by identifying longevity factors and subsequently using it to immortalize aged SMPs, we can restore the regenerative capacity of aged SMPs. We aim to identify targets for rejuvenation of sarcopenic skeletal muscle. In order to achieve this, we intend to first replicate our successes with immortalization in aged and sarcopenic muscle.
Following isolation, a number of validation studies will be performed to confirm that these isolated cells are indeed SMPs. After validation, sarcopenic and control healthy SMPs will be subjected to transduction of unique cocktail of transgenes using our previously published methods. A successful transgenic combination is one that rejuvenates aged SMPs and maintains the ability to differentiate into myotubes. Once achieved, the rejuvenated aged SMPs and primary sarcopenic aged myoblasts and myotubes will be subjected to RNA-sequencing and metabolomics in order to identify the underlying mechanisms that drive rejuvenation. Upon identification of the pathways involved, we will perform a targeted screen from small molecules that can modulate these pathways. From these investigations, we hope to derive a working model as well as viable targets for the rejuvenation of sarcopenic myoblasts.
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