June 22nd, 2026
Klotho is one of the few robustly longevity-associated genes. The effects of increased klotho expression on life span in mice that are arguably large enough to be interesting even if one prefers more of a focus on damage repair in the treatment of aging. A number of companies are developing therapies based on either the delivery of klotho fragments shown to improve function in aged animals, or using gene therapies to promote klotho expression and secretion. While klotho is important in the aging kidney, it is the ability of circulating klotho to promote function in the aging brain that has attracted greater interest, perhaps in large part because the biochemistry of its influence on the brain is less well understood.
Brain aging is accompanied by progressive disturbances in calcium signaling, mitochondrial function, redox balance, neuroimmune regulation, and barrier-fluid homeostasis, collectively increasing susceptibility to neurodegenerative diseases. Therefore, identifying physiological regulators that stabilize these interconnected processes is central to understanding brain aging. Klotho, an antiaging protein initially characterized by its systemic roles in mineral metabolism and lifespan regulation, has emerged as a key modulator of cellular and tissue homeostasis across multiple organs, including the central nervous system.
