Cellular senescence is a key contributor to aging and aging-related diseases, but its metabolic profiles are not well understood. Here, we performed a systematic analysis of the metabolic features of four types of cellular senescence (replication, irradiation, reactive oxygen species [ROS], and oncogene) in 12 cell lines using genome-wide metabolic modeling and meta-analysis. We discovered that replicative and ROS-induced senescence share a common metabolic signature, marked by decreased lipid metabolism and downregulated mevalonate pathway, while irradiation and oncogene-induced senescence exhibit more heterogeneity and divergence. Our genome-wide knockout simulations showed that enhancing the mevalonate pathway, by administrating mevalonate for instance, could reverse the metabolic alterations associated with senescence and human tissue aging, suggesting a potential anti-aging or lifespan-extending effect. Indeed, the experiment in Caenorhabditis elegans showed that administrating mevalonate significantly increased the lifespan. Our study provides a new insight into the metabolic landscape of cell senescence and identifies potential targets for anti-aging interventions.

Rosacea, as a progressive and chronic inflammatory skin disease, lacks safe and effective treatment options. Our previous study reported metabolic disturbance in rosacea patients, containing abnormal lipid metabolism. Building on this, we characterized significant alterations in fatty acid metabolism among rosacea patients, with a notable increase in linoleic acid (LNA) levels. We further demonstrated that LNA prevents rosacea-like dermatitis in LL37-induced rosacea-like mouse model. Our evidence indicated that LNA hyperactivates PPARγ signaling in the epidermis, a phenomenon observed in both rosacea patients and mouse model. Inhibiting PPARγ rescued the effect of LNA in LL37-induced mice. Additionally, our in vivo and in vitro evidence strongly supported the presence of mitochondrial damage in the keratinocytes of rosacea. LNA stimulated PPARγ to reduce the reactive oxygen species production, increasing the generation of ATP and recovering mitochondrial membrane potential. Finally, through a prospective cohort study utilizing UK Biobank data and linkage disequilibrium score regression (LDSC) regression analysis, we further confirmed LNA levels are negatively related to the risk of rosacea, highlighting LNA as a promising therapeutic strategy for rosacea treatment.

Aging is commonly associated with the decline in the function of tissues and organs, along with increased prevalence of age-related diseases. At the "International Symposium on Aging and Rejuvenation" hosted by the Institute of Zoology, Chinese Academy of Sciences, a panel of experts convened to delve into critical topics, including the biomarkers indicative of aging and the factors that accelerate this process. Throughout the symposium, each expert presented their research findings and offered profound insights into the mechanisms, biomarkers, and potential interventions for combating aging. Here, several of the editorial board members at the symposium answer the questions posed by Life Medicine.

Gut organoids are 3D cellular structures derived from adult or pluripotent stem cells, capable of closely replicating the physiological properties of the gut. These organoids serve as powerful tools for studying gut development and modeling the pathogenesis of intestinal diseases. This review provides an in-depth exploration of technological advancements and applications of gut organoids, with a focus on their construction methods. Additionally, the potential applications of gut organoids in disease modeling, microenvironmental simulation, and personalized medicine are summarized. This review aims to offer perspectives and directions for understanding the mechanisms of intestinal health and disease as well as for developing innovative therapeutic strategies.