Kang Shuai Lao Pian exerts anti-aging effects by enhancing mitochondrial oxidative metabolism

Mitochondrial dysfunction is regarded as a central node in the network of senescence markers. Therefore, rebuilding mitochondrial function is crucial for slowing down the aging process in multiple organs. Kang Shuai Lao Pian (KSLP), a traditional herbal formula with anti-aging properties, has multiple pharmacological effects. Nevertheless, the impact of KSLP on the overall aging state and mitochondrial function has not been explored.

The purpose of this study was to uncover the effects of KSLP on the overall aging state and reveal the underlying mechanism through which KSLP exerts its effects.

We constructed aged mouse models to evaluate the multidimensional efficacy of KSLP. Subsequently, with the help of multi-omics joint analysis technology, we predicted the potential targets of the KSLP in modulating the aging of the heart, brain, and gastrocnemius. Finally, we employed targeted metabolomic assays, qRT-PCR, and western blot to validate the molecular mechanism underlying KSLP treatment in aging.

We observed that Kang Shuai Lao Pian alleviated the aging-associated phenotypes across the heart, brain, and gastrocnemius by altering seven aging hallmarks, including mitochondrial dysfunction, deregulated nutrient-sensing, intercellular communication, etc. Notably, multi-organ integration analysis identified the Oxidative phosphorylation (OXPHOS) pathway, widely regulated by KSLP in individual tissues, as the core pathway for delaying aging. We further elucidated that KSLP resets the OXPHOS pathway and promotes pyruvate oxidation, improving the coupling of glycolysis and glucose oxidation to maintain myocardial mitochondrial oxidative metabolism.

Our work highlights that KSLP promotes mitochondrial rejuvenation in aged mice by coordinately enhancing pyruvate oxidation capacity and electron transport chain (ETC) efficiency. Furthermore, we reveal the molecular landscapes by which KSLP regulates aging in diverse organs, offering a promising strategy for maintaining mitochondrial oxidative metabolism and delaying aging.