l defenses should be a lot more effective with regard to the diverse ailments related to energy metabolism and aging (e.g., metabolic syndrome which includes T2DM, dyslipidemia and steatohepatitis, and frailty in aging, such as cognitive impairment, cachexia and sarcopenia).Supplementary Supplies: The following are readily available on the web at mdpi/article/ ten.3390/nu14010107/s1, Figure S1: AX elevated NAD+ levels in C2C12 myoblasts. Figure S2: AX prevented age related glucose intolerance and insulin resistance in male C57BL/6J mice fed a normal diet regime (NC). Figure S3: Impact of AX on respiratory activity of isolated mitochondria from mouse liver. Author Contributions: Y.N., A.N., K.H. and K.T. wrote the manuscript, contributed to discussion and reviewed/edited manuscript; Y.N. and also a.N. participated in the in vivo and in vitro research shown in “Supplementary Materials”. Y.N. as well as a.N. analyzed the information, and Y.N. performed the statistical analysis. All authors contributed to discussion, laboratory assistance, and reviewed/edited the manuscript. K.T. is definitely the guarantor of this work and requires responsibility for the integrity in the data and also the accuracy in the data analysis. All authors have read and agreed for the published version from the manuscript. Funding: “Supplementary Materials” operate was supported by study grants from Japan Diabetes Foundation; the Uehara Memorial Foundation; the Naito Foundation; Translational Study plan, Strategic PRomotion for practical application of Revolutionary medical Technologies (TR-SPRINT) from Japan Agency for Healthcare Study and Development; Toyama New Market Organization; Regional Innovation Method Support Plan of Ministry of Education, mAChR1 Agonist review Culture, Sports, Science and Technology-Japan, Hokuriku Life Science Cluster; Fuji Chemical Industries Co., Ltd.; Japan AstraZeneca K.K.; Merck Co., Inc.; Health-related Assessment Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma; Novo Nordisk Pharma, Ltd.; Kowa Pharmaceutical Co., Ltd.; BRD4 Modulator Accession Astellas Pharma Inc.; Eli Lilly Co., Ltd.; Akurey Marketing and advertising Co., Ltd.; Sanofi Co., Ltd.; Daiichi Sankyo Co., Ltd.; MSD Co., Ltd.; Asahi Kasei Pharma Co., Ltd.; Teijin Pharma Co., Ltd.; Japan Boehringer Ingelheim Co., Ltd.; and Ono Pharmaceutical Co., Ltd. This work was also supported by Grants-in-Aid for Japan Society for the Promotion of Science (JSPS) Fellow (18F18102 to A.N). Besides the above, this study has not received any external funding. Institutional Critique Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: All data underlying the results are obtainable as part from the report and no further source data are essential. Acknowledgments: The authors would prefer to thank the research assistants Ayaka Nishi, Yurie Iwakuro, Qun Zhang and Kana Sugihara at the Initially Department of Internal Medicine, Faculty of Medicine, University of Toyama. We would prefer to thank Takashi Nakagawa, Kunimasa Yagi, Shiho Fujisaka, Tomonobu Kado, Akiko Takikawa, Keiichi Koizumi, Hisashi Mori, Tsutomu Wada, Toshiyasu Sasaoka and Manabu Ishiki at University of Toyama, Isao Usui, Aminuddin Aminuddin, Arshad Mahmood, Vincent Wood, Arun Nair, e Lignell, Joerg Schnackenberg, Hidehiko Takagi, Wataru Miki, Hideki Hashimoto, Eiji Yamashita, Yasuhiro Onogi, Hirohumi Ogawa, Toshinari Takamura, Tsuguhito Ohta, Yuji Naito, Takashi Maoka, Norihiko Misawa, Masashi Hosokawa, Akiyoshi Sawabe, Hedeyuki Sakaki, Sadawo Komemushi, Yasuhiro Furuichi, Jiro Takahashi, Aki