Comparative Analysis of Yukmijihwang-tang and Palmijihwang-tang: Lifespan Extension and Kidney Function Improvement in Aging Models

Aging is associated with a decline in physical and mental functions, necessitating support strategies to extend the healthy life expectancy (HLE). Traditional Asian herbal medicines, such as Yukmijihwang-tang (YM) and Palmijihwang-tang (PM), are used to enhance HLE by improving the kidney function and treating age-related conditions. In this study, we aimed to investigate the effects of YM and PM on lifespan extension and kidney aging marker and aging-related gene expression levels in mice and elucidate the underlying hormonal mechanisms. A lifespan assay was conducted using Caenorhabditis elegans to compare and analyze the effects of YM and PM on HLE and kidney function. Subsequently, aging markers and kidney function were analyzed in aged mice treated with YM and PM. Additionally, RNA sequencing of kidneys was performed to analyze the RNA expression levels related to the hormonal pathways of YM and PM. YM and PM significantly increased the lifespan of C. elegans in a dose-dependent manner. In aged mice, YM and PM restored the kidney aging markers, including the plasma klotho and albumin levels, glomerular filtration rate, urine volume, osmolality, and sodium levels. Transcriptomic analysis revealed distinct gene expression patterns. Although both YM and PM regulated similar pathways, PM affected 4.5-times more genes associated with the mitochondria, endoplasmic reticulum, and their membranes than YM. Furthermore, YM and PM modulated the hormone metabolism genes associated with longevity, highlighting their potential to mitigate age-related conditions through diverse molecular pathways. This study demonstrated the potential of YM and PM to extend HLE by modulating gene expression and improving kidney function, thus providing promising natural therapeutics with few side effects.