Longevity: Klotho, the long-lived protein. What it is and how it works

Giacomo Martiradonna

May 7 – 12.16pm – MILAN

In the Greek pantheon, Klotho she was the youngest of the three Fates, the divinities who weaved the destiny of men. An evocative name, chosen for a protein discovered in 1997 which, like the thread woven by Moira, seems to play a role fundamental in determining the length of human life. Klotho is in fact a transmembrane protein, encoded by a gene present on chromosome 13, which appears to play a key role in slow down aging and in counteracting the onset of various age-related pathologies. Its influence on longevity has been widely demonstrated by studies on animal models. Mice with higher levels of Klotho lived significantly longer and had a lower risk of developing diseases such as diabetes, osteoporosis and Alzheimer’s. But the charm of Klotho does not end there: this protein would appear to be a real one biomarker of biological agea more precise indicator of chronological age for assessing an individual’s health status.

klotho, longevity protein

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We know that the concentration of Klotho in the blood tends to decrease with advancing age; this suggests that monitoring its levels could provide valuable information on real condition of an organism. But Klotho could do much more: he could even become a potential therapeutic target. In short, the hypothesis is that by modifying the levels of this protein, through targeted pharmacological interventions or lifestyle changes, it could be possible slow down aging.

The mechanism of action of Klotho is not yet completely clear, but it is hypothesized that it plays a key role in the regulation of different cellular processes that affect senility, including:

• calcium homeostasis: Klotho modulates the activity of ion channels that control the flow of calcium in cells. This helps protect cells from damage caused by excess calcium, a factor that contributes to aging and age-related diseases. Its activity also appears to be related to the negative regulation of the synthesis of active vitamin D, which directly influences calcium and phosphorus metabolism;
• insulin sensitivity: Klotho increases the sensitivity of cells to insulin, the hormone that regulates glucose metabolism, which in turn counteracts the onset of diabetes;
• oxidative stress: Klotho activates the production of antioxidant enzymes, which fight cell-damaging free radicals;
• cellular senescence: Klotho slows the cellular aging process, whereby cells cease to divide and function properly. As a result, tissues remain healthy and functioning longer.

research

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In mice lacking Klotho, a accelerated agingcharacterized by:

• arteriosclerosis: plaque buildup in the arteries, which can lead to heart attacks and strokes;
• reduced cardiovascular function: impairment of the ability of blood vessels to dilate and decreased formation of new blood vessels;
• multiple organ degeneration: damage to kidneys, lungs and heart;
• increase in mortality: Mice lacking Klotho die at a young age.

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Studies seem to suggest that Klotho plays a vital role in protection from aging and from senile diseases but further research will be necessary to fully understand the mechanisms of action of this extraordinary protein and, above all, to develop potential therapies. “From mice to chimpanzees up to higher mammals such as man, it has unequivocally been found that, when we have levels of this protein reduced compared to the average level relating to one’s chronological age, life expectancy is reduced“, he explains to Corriere della Sera Ascanio Polimeni, neuroendocrinologist, director of LongevYa Project and Regen4Life Research Group. “And we see more easily theonset of dementia, cardiovascular diseases, tumors, accelerated aging from all points of view, from skin, to hair, to osteoporosis, to loss of muscle mass up to disability and therefore a anticipated mortality“, he concludes.