Anti-aging effect of pyruvate via control of mitochondrial and lysosomal function in the dermal fibroblasts
Jeong Yeon Kim2, Sung Hoon Lee1, Il-Hong Bae1, Dong Wook Shin1, Daejin Min1, Mira Ham1, Kyu-Han Kim1, Tae Ryong Lee1, Hyoung-June Kim1, Yeong Wook Song2*, In Sup Kil1*
1Basic Research & Innovation Division, Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, 17074, Republic of Korea; 2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea
*Corresponding Author: firstname.lastname@example.org, email@example.com
Mitochondrial dysfunction can drive cellular senescence, which accompanied by change of metabolism and increase in a senescence-associated secretory phenotype (SASP). Although pyruvate, a key metabolite for numerous aspects of metabolism, has been used as general supplement in synthetic medium, the physiological function of pyruvate underlying its anti-aging effects under normal conditions has remained unknown. Here, we show that extracellular pyruvate prevents senescence of normal human dermal fibroblasts (NHDFs) through increase of NAD+ generated during conversion to lactate. Acetylated PGC-1α, v-ATPaseV0A1, RelA, and histoneH3 accumulate under pyruvate deprivation conditions, resulting in the onset of senescence in NHDFs through accumulation of abnormal mitochondria generated by lysosomal inactivation-induced mitophagy defects, and through increase in SASP. Furthermore, pyruvate showed anti-aging effects in the SEs model, which consists of a dermis and epidermis similar to in vivo skin tissue. Our findings reveal a new connection between pyruvate and mitochondrial dysfunction related to aging. These results suggest that the pyruvate deprivation-induced senescence provides a model that can be used to study the connection between metabolism and aging under normal conditions.