Jun Li, PhD | Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; Zheng Wang, PhD; Xiaoqian Zhang, PhD; Na Liang, PhD; Qing Tan, MD; Wenbin Liu, BS
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2022
Aging is one of major factors that account for skeletal muscle mass loss and dysfunctions. So far, there is no practically efficient method to ameliorate skeletal muscle degeneration caused by aging. Supplementing NAD+ is a newly emerging strategy that has shown promising effects in slowing down aging-related muscle dysfunctions. The previous work of our team showed that increasing NAD+ in naturally aged mice or premature aging mice model by injecting NMN had improved muscle functions, yet which were not reproduced in C2C12 cells if directly adding NMN into the culture media. Based on this, we hypothesize that NAD+ ameliorates age-related muscle dysfunctions by regulating the secretion of adipokines in vivo. In this project, we first identify the key factor secreted by adipose tissues as SPN, which is responsible for the beneficial effects in muscles due to NMN injection; and then uncover the mechanism by which this key adipokine under the influence of NAD+ regulates the metabolism and fiber types remodeling of skeletal muscles, along with dissecting the signal pathways involved; subsequently, we verified the therapeutic effect of improving muscle functions by supplementing this particular adipokine in naturally aged mice and Sarcopenia mice model; finally complete the clinical verification of the correlation between SPN and sarcopenia.This project reveals the very first evidence for the inter-tissue crosstalk between muscle and adipose mediated by NAD+ and provides a new option for sarcopenia therapeutic intervention.
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