What is Klotho?
This vital protein gets its name from Clotho, a Greek goddess and one of the three fates, who, according to myth, spins the thread of life. This connection highlights Klotho’s vital link to longevity
Greek Gods and Goddesses – Clotho spins the web of life
Klotho and Healthy Aging
Klotho is essential to overall health and longevity. Studies in mice demonstrated that those lacking Klotho aged prematurely and lived shorter lives. In humans, research indicates that lower Klotho levels are associated with an increased risk of developing age-related conditions, including:
- Cardiovascular disease
- Cancer
- Kidney disease
- Diabetes
- Alzheimer’s disease and dementia
- Osteoporosis
- Autoimmune disorders
- Depression
Conversely, individuals with higher Klotho levels often experience greater longevity and a longer healthspan—the number of years they live in good health.
The Two Forms of Klotho
Klotho exists in two primary forms in the body:
Membrane-bound Klotho: This form is attached to the surface of cells, especially in the kidneys. It works closely with a hormone called fibroblast growth factor 23 (FGF23), which is mainly produced in the bones. This partnership is crucial for regulating phosphate and vitamin D levels, both vital for strong bones and overall health.[1, 2]
Soluble Klotho (s-Klotho): This form circulates freely in the blood, urine, and cerebrospinal fluid (the fluid around the brain and spinal cord). It’s created when certain enzymes cut the membrane-bound form. Soluble Klotho acts like a hormone, delivering its beneficial effects to various organs and tissues throughout the body. [3, 4].
How Klotho Promotes Health
Klotho contributes to health and longevity in several significant and complex ways:
- Mineral Balance: Especially in its membrane-bound form, Klotho helps control the levels of calcium, phosphate, and vitamin D in the blood. This is vital for strong bones and can help prevent issues like kidney stones [1, 5].
- Blood Sugar Control: Klotho interacts with insulin receptors, improving how the body uses insulin. This helps manage blood sugar levels and can protect against diabetes [5].
- Cell Health: Klotho supports cell growth and helps cells survive by activating beneficial signaling pathways and preventing harmful ones [6].
- Protection from Damage: With its antioxidant and anti-inflammatory properties, Klotho helps protect cells from damage. It can boost protective enzymes and reduce inflammation [6, 7].
- Inhibiting Aging Pathways: Notably, Klotho has been shown to slow down key pathways linked to aging, such as TGF-β, IGF-1, Wnt, and NF-κB. These pathways can lead to cellular aging, programmed cell death, inflammation, and tissue scarring. By regulating these, Klotho helps maintain healthy cells and tissues [6, 7, 8].
Research and Therapeutic Potential
Researchers are actively exploring ways to increase Klotho levels as a potential treatment for many age-related diseases. Some strategies under investigation include:
- Gene Therapy: Delivering genes that tell the cells to produce more Klotho protein. Studies in mice have shown that increasing soluble Klotho through gene therapy can extend lifespan and improve physical and cognitive health [6, 12].
- Direct Protein Administration: Giving Klotho protein directly as a medication. The challenge here is to deliver it to the correct organs efficiently [6].
- Pharmacological Approaches: Identifying compounds that can naturally stimulate Klotho production or mimic its effects. For example, some studies suggest that exercise, certain medications (like ACE inhibitors, statins, and some antidiabetic drugs), and even certain supplements can influence Klotho levels [13, 14].