Klotho

Why is Klotho important for your Healthspan?

Hormones — Longevity

Klotho is one of the most studied “longevity genes” because of its profound influence on cellular aging, cognitive function, and metabolic control. Higher Klotho levels are associated with improved kidney function, reduced inflammation, enhanced insulin sensitivity, and stronger neuroprotection. Conversely, lower levels correlate with accelerated biological aging, frailty, cardiovascular disease, osteoporosis, and diminished cognitive performance. Tracking Klotho provides rare insight into how well your body maintains resilience across multiple organ systems as you age.

From a disease-prevention perspective, Klotho acts as a systemic regulator of oxidative stress and inflammatory signaling — two of the most important drivers of chronic disease and aging. Reduced Klotho expression has been linked to faster telomere shortening, impaired repair of DNA damage, and diminished mitochondrial function. Clinically, low Klotho can present as early cognitive decline, decreased physical performance, higher blood pressure, or increased vulnerability to metabolic dysfunction. Maintaining higher Klotho levels is associated with greater longevity and more years lived in good health.

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What is Klotho?

Klotho is a hormone-like protein encoded by the KL gene and expressed primarily in the kidneys and brain. It circulates in the bloodstream and acts as a key regulator of phosphate balance, vitamin D activation, insulin signaling, and calcium homeostasis. Functionally, Klotho serves as a co-receptor for fibroblast growth factor 23 (FGF23), helping maintain mineral metabolism and kidney filtration efficiency. Beyond these metabolic roles, Klotho exerts protective effects across the brain and cardiovascular system by reducing oxidative stress, suppressing inflammatory pathways, and enhancing synaptic function.

At the cellular level, Klotho influences major aging pathways, including IGF-1 signaling, Wnt signaling, and the regulation of reactive oxygen species. Its decline with age is thought to contribute to progressive loss of tissue repair capacity and increased disease vulnerability. Measuring Klotho offers a window into how effectively your body maintains youth-promoting molecular processes such as mitochondrial efficiency, neural plasticity, and systemic stress resistance.

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How do we take action?

Exercise Improvement — Stress Reduction — Sleep Optimization

Strategies that support Klotho expression focus on reducing metabolic stress and improving whole-body regenerative capacity. Regular aerobic and resistance exercise has been repeatedly shown to elevate circulating Klotho levels, likely through improved mitochondrial function and enhanced cellular repair signaling. High-quality sleep further sustains Klotho activity by lowering inflammation and supporting hormonal balance, particularly growth hormone and cortisol rhythms. Managing chronic stress through meditation, breathwork, or restorative practices can also protect Klotho signaling, as elevated cortisol has been linked to accelerated Klotho decline.

Additionally, maintaining healthy vitamin D levels, avoiding smoking, moderating alcohol intake, and supporting kidney health through hydration and nutrient-dense eating can help protect long-term Klotho function. When levels are persistently low, medical follow-up can guide deeper evaluation of kidney function, endocrine status, and metabolic risk factors that may be contributing to reduced Klotho expression.

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Additional resources

1. Hu, M. C., Shi, M., Cho, H. J., et al. (2013). Klotho and aging. Biochimica et Biophysica Acta (BBA) - General Subjects, 1830(2), 482–494. https://doi.org/10.1016/j.bbagen.2012.11.013
2. Kurosu, H., & Kuro-o, M. (2008). The Klotho gene family and the endocrine fibroblast growth factors. Current Opinion in Nephrology and Hypertension, 17(4), 368–372. https://doi.org/10.1097/MNH.0b013e328302c6d4

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