Fight Aging!

Increased klotho expression increases longevity in mice, while reduced klotho expression accelerates aging. The most well studied effects of klotho on organ function involve the kidney and brain, where in both cases it appears protective via a number of different mechanisms. Unfortunately, klotho expression declines with age. Whether treating humans with therapies that increase levels of klotho will produce effects that are as large as those observed in mice remains to be seen. Programs that might lead to treatments remain at a preclinical stage of development, though recently advanced to the point of testing in non-human primates.

The circulating levels of soluble Klotho have been observed to decrease with age, which increases the risk of age-related illnesses. Researchers demonstrated accelerated aging and a shortened lifespan in mice when the Klotho gene was silenced or deficient. In contrast, an extended lifespan was seen when the gene was overexpressed. Likewise, in humans, Klotho has been shown to display many beneficial effects, especially related to anti-aging. Although the membrane-bound Klotho protein was first associated with neurodegenerative diseases, it has been linked to various other age-related disease processes, including cancer biology and cardiovascular, renal, and skin diseases.

Klotho plays a role in cancer biology by serving as both a tumor suppressor and prognostic tumor biomarker, thus preventing and detecting neoplasms. Furthermore, Klotho overexpression (KL-OE) reduces the number of cancer cells that survive. Treatment with soluble Klotho has been shown to reduce tumor volume in preclinical cancer models in organs such as the stomach, pancreas, colon, and breast. Concerning the link between cardiovascular illness and Klotho, researchers discovered that decreased cardiac Klotho expression and increased cardiac fibroblast growth factor (FGF) expression lead to higher cardiovascular risk. Klotho can be used as an early and sensitive biomarker for kidney illnesses, as well as a potential treatment for both acute kidney injury and chronic kidney disease (CKD). It is also protective against ultraviolet B (UVB)-induced damage, and its overexpression can considerably alleviate the UVB-induced damage to cells, an effect which can be seen with aging.

Klotho has positive benefits on the neurological system by causing a higher representation of useful longevity genes, preventing further neuronal damage, and offering neuroprotection. Thus, it has the potential to become a new treatment for many age-related diseases that cause dementia, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In this review, we discuss the mechanisms of Klotho's benefits and roles on various organ systems, specifically on nervous system disorders that lead to dementia.

Link: https://doi.org/10.7759/cureus.40043