Fight Aging!

Researchers here note changes in the nucleolus in both old cells and cells from progeria patients, and suggest that these changes may be characteristic enough in normal aging to serve as a biomarker to assess biological age. There is great interest in the research community in establishing a low-cost, reliable biomarker of this nature, as it would considerably speed up the assessment of potential rejuvenation therapies, those that address the root causes of aging. Currently it is an expensive and time-consuming process, as studies must run long enough to observe the results of a treatment upon mortality rates.

Progeria is not accelerated aging, but has superficially similar outcomes. This rare condition is of interest because the form of molecular damage that is prevalent in this condition, mutated lamin A that causes structural and other irregularities in cells, is also found to a small degree in normal aging. It is an open question as to whether or not that matters in comparison to the laundry list of other forms of molecular damage found in old tissues. So secondary effects observed in progeria patients, those downstream of the lamin A issue, may well not be in any way relevant to normal aging. Even if the observation dovetails with existing knowledge, as is the case here, it could still be peculiar to the progeroid tissue environment and its particular distribution of forms of cellular damage, and so caution is required. Still, the findings in normal cells carried out as a part of this study are intriguing.

Scientists have found that protein synthesis is overactive in people with progeria. The work 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. 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."

Initially, researcher were interested in whether 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. "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 progeria cells. 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 showing that decreasing protein synthesis extends lifespan in roundworms and mice. The researchers plan to continue studying how nucleolus size may serve as a reliable biomarker for aging.

Link: http://www.salk.edu/news-release/protein-turnover-clue-living-longer/