The Klotho gene, first identified in 1997, takes its name from Greek mythology.
Klotho was a Greek goddess, the youngest of the three Fates, who determined the lifespan of every mortal. Klotho would spin the thread of life; Lachesis would measure it; Atropos would cut it.
The Klotho family of genes has been clearly identified for its role in regulating the ageing process and age suppression. Overexpression of these proteins has been shown to extend lifespan in various animal studies.
They serve a variety of functions, from the metabolism of vitamin D, phosphate and calcium, to reducing oxidative stress, as well as offering neuroprotective effects, all of which play a major role in the ageing process.
Vitamin D indirectly regulates Klotho expression, largely through UV exposure from sunlight and the activated form of vitamin D, calcitriol (the active metabolite of vitamin D3). This may help explain why vitamin D deficiency is associated with cardiovascular disease and accelerated ageing.
Klotho has also been identified as a key regulator of calcium and phosphate absorption and overall homeostasis, which, alongside vitamin D, also underlines its importance for bone strength and health.
So, apart from vitamin D, are there other ways to increase Klotho expression? Yes. Short-interval, high-intensity exercise has also been shown to increase Klotho expression, suggesting that sunlight and exercise together may help slow the sands of time.
Klotho also increases expression of another well-established longevity gene, FOXO3a, suggesting Klotho may help suppress reactive oxygen species (ROS)-related oxidative stress.
FOXO3 helps activate and upregulate a variety of antioxidant genes, serving a function similar to consuming antioxidant-rich foods. One of these is an important mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD).
We can also activate FOXO3 through a few simple dietary and lifestyle changes. EGCG (epigallocatechin gallate), found in white and green tea, and quercetin, found in white onions, have both been associated with increased FOXO3 expression.
Heat stress, such as that experienced in saunas, may also activate FOXO3, as it supports the expression and activation of heat shock proteins (HSPs), which help repair damaged DNA and proteins.
A study in Finland found a 24% reduction in all-cause mortality among men who used a sauna 2–3 times per week, alongside reductions in cardiovascular disease, cancer mortality and stroke risk.
Light exercise is another way to support HSP activation, as raising core body temperature helps trigger their expression too.
