Protein turnover could be clue to living longer

August 30, 2017
Overactive protein synthesis found in premature aging disease may also play role in normal aging. Nucleoli in the cell nucleus, stained bright magenta and cyan against the purple backdrop of the nucleus, are enlarged in the progeria cell (right) compared to the normal cell (left). Credit: Salk Institute

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 synthesis is overactive in people with progeria. The work, described in Nature Communications on August 30, 2017, 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 forcells ," says Martin Hetzer, vice president and chief science officer ofthe Salk Institute and senior author of the paper. "When a cell devotesvaluable resources to producing protein, other important functions may beneglected. Our work suggests that one driver of both abnormal and normalaging 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 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.

Salk scientists explain why protein turnover could be usefulmarker for aging. Credit: Salk Institute

"We analyzed all the proteins of the nucleus and instead of seeing rapid turnover in just mutant lamin A and maybe a few proteins associated with it, we saw a really broad shift in overall protein stability in the cells," says Buchwalter. "This indicated a change in protein metabolism that we hadn't expected."

Along with the rapid turnover of proteins, the team found that the nucleolus, which makes protein-assembling structures called ribosomes, was enlarged in the prematurely aging cells compared to healthy cells.

Even more intriguing, the team found that nucleolus size increased with age in the healthy cells, suggesting that the size of the nucleolus could not only be a useful biomarker of aging, but potentially a target of therapies to counter both premature and normal aging.

The work supports other research that appears in the same issue showingthat decreasing extends lifespan in roundworms and mice.The Hetzer lab plans to continue studying how nucleolus size may serve asa reliable biomarker for aging.

"We always assume that aging is a linear process, but we don't know that for sure," says Hetzer, who also holds the Jesse and Caryl Philips Chair. "A biomarker such as this that tracks aging would be very useful, and could open up new ways of studying and understanding aging in humans."

Explore further: Artificial blood vessels mimic rare accelerated aging disease

More information: Abigail Buchwalter et al. Nucleolar expansion and elevated protein translation in premature aging, Nature Communications (2017). DOI: 10.1038/s41467-017-00322-z , www.nature.com/articles/s41467-017-00322-z

Related Stories

Artificial blood vessels mimic rare accelerated aging disease

August 15, 2017
Biomedical engineers have grown miniature human blood vessels that exhibit many of the symptoms and drug reactions associated with Hutchinson-Gilford Progeria Syndrome—an extremely rare genetic disease that causes symptoms ...

Researchers develop technology to make aged cells younger

July 31, 2017
Aging. We all face it. Nobody's immune and we've long tried to reverse it, stop it or just even slow it down. While advances have been made, true age-reversal at a cellular level remains difficult to achieve. By taking a ...

Researchers describe mechanism behind progeria

October 6, 2015
Progeria, a premature aging disease, is the research focus of Roland Foisner's team at the Max F. Perutz Laboratories of the University of Vienna and the Medical University of Vienna. Children suffering from progeria die ...

Possible new drug for children with progeria

June 30, 2011
(Medical Xpress) -- A new study published in the journal Science Translational Medicine shows that rapamycin and its derivative everolimus, which is currently used to treat cancer and transplant rejections, may work to reverse ...

Scientists create new genetic model of premature aging diseases

April 29, 2011
Working with a group of national and international researchers, scientists from the Florida campus of The Scripps Research Institute have developed a new genetic model of premature aging disorders that could shed light on ...

Recommended for you

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Age and gut bacteria contribute to multiple sclerosis disease progression

November 17, 2017
Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to multiple sclerosis (MS) disease onset and progression.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.