Klotho

Klotho

Klotho is a protein that in humans is encoded by the KL gene. It is named after the Greek goddess Clotho, who was responsible for spinning the thread of life. Klotho is a type-I membrane protein that is predominantly expressed in the kidney and brain. It plays a significant role in the regulation of aging and the maintenance of various physiological processes.

Structure

Klotho is a single-pass transmembrane protein with a large extracellular domain. The extracellular domain can be cleaved and released into the circulation, where it acts as a hormone. The protein consists of two internal repeats, KL1 and KL2, which are similar to glycosidases but lack enzymatic activity.

Function

Klotho functions as a co-receptor for fibroblast growth factor 23 (FGF23), a hormone involved in phosphate and vitamin D metabolism. It also has independent roles in regulating ion channels, insulin signaling, and oxidative stress.

Role in Aging

Klotho has been implicated in the regulation of aging. Mice deficient in Klotho exhibit a syndrome resembling human aging, with symptoms such as arteriosclerosis, osteoporosis, and skin atrophy. Conversely, overexpression of Klotho in mice extends their lifespan.

Metabolic Regulation

Klotho influences calcium and phosphate homeostasis by modulating the activity of FGF23. It also affects insulin signaling pathways, potentially impacting glucose metabolism and insulin sensitivity.

Neuroprotection

Klotho has neuroprotective effects, possibly through its antioxidant properties and its ability to modulate synaptic function. It is being studied for its potential role in neurodegenerative diseases such as Alzheimer's disease.

Clinical Significance

Alterations in Klotho expression have been associated with various diseases, including chronic kidney disease, cardiovascular disease, and cancer. Low levels of circulating Klotho are linked to increased mortality and morbidity in these conditions.

Research Directions

Current research is focused on understanding the molecular mechanisms of Klotho action, its potential as a biomarker for aging and disease, and its therapeutic potential in age-related diseases.

Also see

• Fibroblast growth factor 23
• Aging
• Chronic kidney disease
• Neurodegenerative diseases

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