Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605014, India

Klotho, an anti-aging protein (soluble or membrane-bound) plays a prominent role in understanding the aging process. It exerts various protective activities for neurons and multiple organs. Klotho-deficient mice show accelerated aging and Klotho overexpression prolongs lifespan. The altered expression of Klotho produces premature aging syndrome in humans and various neurological dysfunctions such as cognitive deficits. It reduces oxidative stress and cell death by suppressing the insulin-like growth factor–1 signaling pathway, and consist of a neuroprotective effect on hippocampal neurons by preventing amyloid and glutamate toxicity. It usually does this by activating the antioxidant enzyme system. Klotho is a multifunctional protein that controls the metabolism of phosphate, calcium, and vitamin D. For the various functions of Klotho, it became a potential target for the therapeutic approach to eliminate the risky effects of aging. In this review, we have focused on the structure and molecular mechanism of Klotho function with its role in human aging and age-related neurodegenerative disorders