Scientists have revealed the three-dimensional (3D) structure of an anti-ageing protein, that may not only increase human lifespan but also help develop therapies for age-related diseases such as diabetes, obesity and cancers.
The Klotho proteins — alpha and beta — named after the Greek goddess Clotho, who spun the thread of life, play an important role in the regulation of longevity and metabolism.
Both work in tandem with molecules called endocrine FGFs, which regulate metabolic processes in tissues and organs including the brain, liver and kidneys, among other organs. In the study, led by researchers from Yale University, the team found that beta-Klotho is the primary receptor that binds to FGF21 — a key hormone produced upon starvation.
FGF21 has the potential for boosting insulin sensitivity and glucose metabolism, causing weight loss.
This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as Type 2 diabetes in obese patients, the researchers said, in a paper published in the journal Nature.
“Like insulin, FGF21 stimulates metabolism including glucose uptake. In animals and in some clinical trials of FGF21, it shows that you can increase burning of calories without changing food intake, and we now understand how to improve the biological activity of FGF21,” said Joseph Schlessinger, Chair of Pharmacology at Yale School of Medicine in New Haven, Connecticut.
A new variant of FGF21 with 10 times higher potency and cellular activity was also unveiled. By developing drugs that enhance the pathway, Schlessinger said, researchers can target diabetes and obesity.
Conversely, using agents that block the pathway, they also hope to explore therapies for conditions such as liver cancer and bone diseases, among others. “The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward,” Schlessinger said.