Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.

Jing Yu, Xiaoyan Gao, Hang Shi, Lijun Zhang, Wenlong Nie, Ruochen Zhang, Minglv Fang, Ying Liu, Yingxuan Yan, Bingbing Fan, Chengyuan Wu, Cheng Huang, Shengjie Fan

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. · pubmed

Paper

Abstract

Environmental factors are linked to aging and age-related diseases. Emerging evidence suggests that enhancing body's resistance to xenobiotics might be an anti-aging strategy. The constitutive androstane receptor (CAR) regulates drug-metabolizing enzymes and transporters, coordinating metabolism and immune responses to adapt to stress triggered by exogenous exposure. However, the impact of activating CAR on aging remains unknown. In this study, Caenorhabditis elegans (C. elegans), drug-induced premature aging mice, and senescence accelerated P8 (SAMP8) mice are used as models to explore the effects of CAR activation on lifespan and healthspan, along with the underlying mechanisms. The results showed that hCAR agonist CITCO and mCAR agonist TCPOBOP prolonged the lifespan and healthspan in model organism. The longevity effects of CITCO and TCPOBOP were attenuated in CAR homozygous nhr-8/daf-12 mutant C. elegans as well as CAR

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Research summary

The paper claims that activation of the constitutive androstane receptor (CAR) can prolong lifespan and healthspan in model organisms. This research explores a potential mechanism for enhancing resistance to xenobiotics as a strategy for delaying aging, which aligns with the goal of addressing the root causes of aging.

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