Anti-aging: Researchers Discover Structure of Key Hormone

aging woman using canes to walk

The search for the fountain of youth has lasted millennia, but scientists are now one step closer to finding the secret. Researchers at NYU School of Medicine have discovered the molecular structure of a key anti-aging hormone, providing insight into how it helps slow aging and overturning previous ideas about what exactly keeps aging from accelerating.

What Scientists Previously Thought About Aging

In the late 1990s, researchers genetically-manipulated mice to lack either the α-Klotho protein or fibroblast growth factor 23 (FGF23). These mice experienced premature aging, with early heart disease, cognitive decline, and cancer affecting them more than their non-manipulated peers. Clearly, the scientists thought, both of these proteins are longevity factors. With one or the other missing, the aging process accelerates, with unfortunate consequences for the mice. Despite this established understanding, the recent study may have just knocked αKlotho out of the longevity factor club, proving that the protein is not in fact a major anti-aging hormone.

What the Anti-Aging Study Involved

Moosa Mohammadi and colleagues aimed to analyze anti-aging proteins in detail, determining their atomic structure. The researchers sought out FGF23, its receptor protein FGFR, and α-Klotho, settling the proteins out of a solution and organizing them into orderly, repeating crystals. Using X-rays, the researchers examined the reflected patterns to reveal the protein structures.

When the scientists examined the crystal structure of the proteins, the picture became clear. α-Klotho seems to send out a long receptor-binding arm (RBA) to capture the FGFR, and when α-Klotho was missing this arm, the protein failed to capture FGFR or help FGF23. Once α-Klotho and FGFR were bound together using this arm, the researchers showed, there is a groove just the right size and shape to fit the FGF23 hormone.

What the Discovery Means

While scientists previously believed α-Klotho to be an anti-aging factor in its own right, this study seems to suggest it does not act on its own but instead assists FGF23. With α-Klotho helping out, FGF23 and FGFR interact more strongly, enhancing their ability to slow aging. It seems that after FGF23 is released from bone, it travels to other organs through the blood stream. Once there, the hormone docks onto its receptor, with the help of α-Klotho, activating its anti-aging processes. This hormone helps excretion of phosphate from the kidneys while decreasing reabsorption, lowering overall phosphate levels in the body. This helps prevent negative effects of excess phosphate, including oxidative stress, glucose metabolism, and insulin sensitivity, which researchers believe affect the aging process.

In addition to learning more about causes of aging, researchers now have a better idea of how kidney disease leads to heart disease. When diseased kidneys begin to have trouble eliminating phosphate in the urine, FGF23 levels rise in response to these higher phosphate levels. Although α-Klotho is not present in heart tissue, it can reach the heart through circulating body fluids, where it can enable FGF23 signaling just as if it was naturally bound to the tissue. This FGF23 signaling contributes to heart hypertrophy, abnormal thickening of heart tissue.

The findings may also have implications for diabetes and obesity. The scientists suggest a closely-related protein, β-Klotho, interacts in the same way with its counterpart, FGF21. This hormone helps maintain blood sugar and fatty acid balance.

The Future of Anti-Aging Treatments

The researchers suggest their discovery could pave the way for future anti-aging treatments. Pharmaceutical companies could develop a novel agent to increase or decrease the FGF23- α-Klotho signaling. Increasing the signaling could help protect against aging while decreasing the signal could help prevent heart hypertrophy. The researchers have already used a peptide which is part of the FGF23 hormone to compete with the entire FGF23, reducing its signal to prevent heart hypertrophy in mice.

Have Researchers Really Just Found the Key to Youth?

Although the findings are promising, researchers do not have the cure for aging just yet. Slowing aging itself would help reduce the incidence of heart disease, cancer, kidney disease, dementia, and more, helping prevent these diseases instead of just treating them as they appear. However, this is just one piece of the aging puzzle. More research would need to develop viable treatments, along with ensuring the adjustment of hormones would not have unintended consequences. The cure for aging remains a distant dream, but with these discoveries, scientists are one step closer to finding the clinical fountain of youth.

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