Lithocholic Acid Phenocopies Anti-Aging Effects of Calorie Restriction, Unlocking Path to Improved Health and Longer Life
A recent study published in Nature has made a groundbreaking discovery in understanding the secret to improved health, stronger muscles, and longer life through a key calorie-restriction metabolite called lithocholic acid (LCA). The research, conducted using metabolomics to investigate how calorie restriction induces metabolic changes, reveals that LCA production is responsible for promoting anti-aging effects.
Calorie restriction has been widely studied as a dietary intervention that promotes various metabolic changes. These changes lead to improved life expectancy and numerous health-related benefits in many organisms, including yeast, mice, flies, nematodes, and primates. A recent randomized clinical trial demonstrated that calorie restriction also improves age-related frailty and disease conditions such as insulin resistance, central obesity, and muscle deterioration.
The study found that the activation of AMP-activated protein kinase (AMPK), an enzyme responsible for maintaining energy balance in cells, plays a crucial role in promoting anti-aging effects associated with calorie restriction. These cellular processes include proteostasis, mitochondrial biogenesis, autophagy, mitohormesis, inflammation, and neurodegeneration.
In a key finding, researchers identified serum metabolites that, when modified by calorie restriction, could be responsible for the beneficial effects at the cellular and organismal levels. Specifically, lithocholic acid was found to activate AMPK in various cell types, including mouse embryonic fibroblasts, primary hepatocytes, human embryonic kidney 293T cells, and primary myocytes.
Further investigation revealed that LCA levels increased significantly in calorie-restricted mice compared to ad libitum-fed controls. When administered alone to aged mice for one month, LCA was shown to improve muscle performance by increasing the number of oxidative muscle fibers and reducing glycolytic fibers. This treatment also improved muscle regeneration after damage in aged mice.
In addition, LCA-treated old mice exhibited improvements in running distance, duration, and grip strength, along with alleviated age-associated glucose intolerance and insulin resistance. Ultimately, the findings suggest that LCA is a key metabolite that phenocopies anti-aging effects of calorie restriction, leading to significant health benefits.
The discovery of such a critical metabolite highlights the importance of understanding the mechanisms behind metabolic adaptations in the body, which ultimately contribute to good health and longevity. As researchers continue to unravel the secrets behind calorie restriction and its associated anti-aging effects, they may uncover new therapeutic targets for promoting healthy aging and disease prevention.