Klotho is a longevity-associated gene that has been under investigation for some years. Increasing its expression lengthens life in mice, while reducing it has the opposite effect. Here is an open access review on the topic with a focus on mechanisms relating to cardiovascular disease (CVD):
Klotho, a gene originally identified in 1997 codifying for a novel anti-aging protein, has been implicated in a multitude of biological processes, most of them related to human longevity. Mice lacking the Klotho gene develop a phenotype similar to premature human aging, which includes endothelial dysfunction, vascular calcification, progressive atherosclerosis and shortened lifespan. A reduction in Klotho levels is observed in chronic kidney disease (CKD) patients, similar to other premature vascular aging diseases, such as hypertension or diabetes mellitus. Even normal aging is associated with a reduction in serum and urine concentration of Klotho.
More recently, the involvement of Klotho in vascular protection through different mechanisms has been demonstrated. These mechanisms include inhibition of oxidative stress, modulation of inflammation or attenuation of vascular calcification. Therefore, Klotho has been suggested as a master regulator of CVD. The disruption in the homeostasis of this factor seems to be a key element in the development of CVD. The reduction of circulating levels of Klotho is associated with the presence and severity of coronary artery disease (CAD) and is also an independent marker of some forms of vascular dysfunction such as arterial stiffness. Likewise, various genetic studies have shown the association between gene variants of human Klotho gene with CAD or stroke.