Hypothesis: Klotho can decouple insulin resistance from the
associated pathophysiology  Nature Precedings DOI: Source: OAI
ABSTRACT A very fundamental paradox of insulin resistance is
that in a wide variety of animal models impairment of insulin
signaling increases life span. But in humans it increases the
risk of a range of fatal disorders. The Klotho protein appears
to resolve this paradox. Overexpression of the Klotho gene
increases longevity in mammals by inducing insulin resistance.
But the Klotho protein is simultaneously anti-inflammatory,
antioxidant and pro-angiogenesis. A number of other studies have
indicated that systemic inflammation, angiogenesis dysfunction
and oxidative stress are the main causes of pathological
complications of diabetes. The Klotho protein has demonstrated
that insulin resistance can be decoupled from these pathogenic
mechanisms and if decoupled it might contribute to longevity in
humans as well. However, insulin resistance has always been
treated as the therapeutic target f