It may seem paradoxical, but studying what goes wrong in rare diseases can provide useful insights into normal health. Researchers probing the premature aging disorder Hutchinson-Gilford progeria have uncovered an errant protein process in the disease that could help healthy people as well as progeria sufferers live longer.
Scientists at the Salk Institute found that protein synthesis is overactive in people with progeria. The work, described in Nature Communications, adds to a growing body of evidence that reducing protein synthesis can extend lifespan – and thus may offer a useful therapeutic target to counter both premature and normal aging.
“The production of proteins is an extremely energy-intensive process for cells ,” says Martin Hetzer, vice president and chief science officer of the Salk Institute and senior author of the paper. “When a cell devotes valuable resources to producing protein, other important functions may be neglected. Our work suggests that one driver of both abnormal and normal aging could be accelerated protein turnover.”
Hutchinson-Gilford progeria is a very rare genetic disease causing people to age 8 to 10 times faster than the rest of us and leading to an early death. The rare mutation occurs in one of the structural proteins in the cell nucleus, lamin A, but it has been unclear how a single defective protein in the nucleus causes the myriad rapid-aging features seen in the disease.
Initially, Salk Staff Scientist Abigail Buchwalter, first author of the paper, was interested in whether the mutation was making the lamin A protein less stable and shorter lived. After measuring protein turnover in cultured cells from skin biopsies of both progeria sufferers and healthy people, she found that it wasn’t just lamin A that was affected in the disease.