Cell aging attenuates cellular functions, resulting in time-dependent disruption of cellular homeostasis, which maintains the functions of proteins and organelles. Mitochondria are important organelles responsible for cellular energy production and various metabolic processes, and their dysfunction is strongly related to the progression of cellular aging. Here we demonstrate that disruption of proteostasis attenuates mitochondrial function before the induction of DNA damage signaling by proliferative and replicative cellular aging. We found that lotus (Nelumbo nucifera Gaertn.) germ extract clears abnormal proteins and agglutinates via autophagy-mediated restoration of mitochondrial function and cellular aging phenotypes. Pharmacological analyses revealed that DAPK1 expression was suppressed in aging cells, and lotus germ extract upregulated DAPK1 expression by stimulating the acetylation of histones and then induced autophagy by activating the DAPK1-Beclin1 signaling pathway. Furthermore, treatment of aging fibroblasts with lotus germ extract stimulated collagen production and increased contractile ability in three-dimensional cell culture. Thus, time-dependent accumulation of abnormal proteins and agglutinates suppressed mitochondrial function in cells in the early stage of aging, and reactivation of mitochondrial function by restoring proteostasis rejuvenated aging cells. Lotus germ extract rejuvenates aging fibroblasts via the DAPK1-Beclin1 pathway-induced autophagy to clear abnormal proteins and agglutinates.
Obesity is characterized by the excessive accumulation of fat to adipose tissue, which is related to abnormal increasing white adipose tissue (WAT) in the body, and it upregulates the risk of multiple diseases. Here, kuanoniamine C, which is a pyridoacridine alkaloid, suppressed the differentiation of pre-adipose cells into white adipocytes via the modulation of mitochondrial function, and inhibited WAT expansion in the early phase of high-fat-diet-induced obesity model. Pharmacological analysis revealed that inhibition of mitochondrial respiratory complex II, which new target of kuanoniamine C, activated reactive oxygen species (ROS)-extracellular signal-regulated kinase (ERK)-β-catenin signaling, and this signaling was antagonized by insulin-, IBMX-, and dexamethasone-induced adipogenesis. Therefore, the kuanoniamine C might prevent abnormal WAT expansion even when eating a diet that is not calorie restricted.
Reactive oxygen species (ROS), such as superoxide, are crucial factors involved in the stimulation of cellular aging. Mitochondria, which are important organelles responsible for various metabolic processes in cells, produce ROS. These ROS impair mitochondrial function, thereby accelerating aging-related cellular dysfunction. Herein, we demonstrated that the Spirulina polysaccharide complex (SPC) restores mitochondrial function and collagen production by scavenging superoxide via the upregulation of superoxide dismutase 2 (SOD2) in aging fibroblasts. We observed that SOD2 expression was linked to inflammatory pathways; however, SPC did not upregulate the expression of most inflammatory cytokines produced as a result of induction of LPS in aging fibroblasts, indicating that SPC induces SOD2 without activation of inflammatory pathways. Furthermore, SPC stimulated endoplasmic reticulum (ER) protein folding by upregulating ER chaperones expression. Thus, SPC is proposed to be an antiaging material that rejuvenates aging fibroblasts by increasing their antioxidant potential via the upregulation of SOD2.
