Current situation and challenge of exogenous 3-hydroxybutyrate derived from polyhydroxyalkanoates for elderly health: A review.

3-Hydroxybutyrate (3HB), predominantly found in the liver, muscles, and brain, is the most important endogenous ketone body in humans. During prolonged fasting and starvation, 3HB can partially replace glucose to meet some of the body's energy needs. In recent years, the resurgence of the ketogenic diet (KD) and systematic exploration of the favorable biocompatibility of polyhydroxyalkanoates (PHAs), the precursor polymer to 3HB, have led to numerous reports indicating that the benefits of exogenous 3HB supplementation outweigh the drawbacks, particularly for middle-aged and elderly individuals. In this review, the physicochemical properties, physiological functions, and biosafety of 3HB in the elderly population are introduced. The effects of exogenous 3HB supplements, including KD, ketone esters, 1,3-butanediol, and ketone salts, on the elderly are compared. It is proposed that exogenous 3HB derived from PHAs is optimal for this population. Exogenous 3HB supplementation for elderly health maintenance and disease treatment is summarized, with an outline of four challenges related to the mechanistic and clinical research of exogenous 3HB supplementation for elderly health. This aims to explore its novel therapeutic potential as a small molecule in the context of aging.