Bile acids, chaperones, and mammalian longevity

Bile acids are detergent molecules derived from cholesterol in the liver that are important for the metabolism and absorption of lipids in the intestine. Bile acids are also steroid hormones activating specific nuclear receptors and G protein-coupled receptors. Conjugated bile acids are cytoprotective and anticarcinogenic. Bile acid synthesis and bile flow decreases markedly during aging. The housekeeping molecular chaperones are stress response proteins, important for the processes of folding, maintenance, and repair of proteins, RNA, and DNA, as well as for the structure and function of the steroid hormone receptors. The level of expression of the molecular chaperones correlates with mammalian longevity as well as with the life span of differentiated cells. The functions of the chaperone machinery are progressively impaired during aging, and the progressive age-related impairment of these housekeeping mechanisms probably contributes to the phenotype of aging. This review presents evidence that the bile acids are chemical chaperones, improving the general chaperone defense, and thus serve to support an epigenetic mechanism of possible significance for the evolution of mammalian longevity, as well as for the attainment of healthy aging.