A new study published by scientists at the Salk Institute recently shows how that changes in the nucleolus of progeria cells and normally aged cells share some characteristics that may allow them to be used as a biomarker for biological age.
What is Progeria?
Hutchinson-Gilford progeria is a rare genetic disease that causes people to suffer from aging-like symptoms on an accelerated timescale compared to regular aging. Whilst it shares similarities with regular aging it is not accelerated aging per se, but the outcome is much the same.
The condition is due to a rare mutation in one of the structural proteins in the cell nucleus, lamin A, but it was not clear how a single defective protein in the nucleus causes the various aging-like features typical of this disease.
The researchers first investigated if the mutation was causing the lamin A protein to become more unstable and thus shorter lived. After measuring the level of protein turnover in progeria cells and healthy cells, they found out that it was not just lamin A that was being affected by the disease.
The looked at all the proteins in the nucleus and rather than just the mutant lamin A experiencing rapid turnover, they saw a wide change in overall protein stability in progeria cells. This was quite a surprise for the researchers and suggests a change in protein metabolism with a broad range of effects just from one mutation to lamin A.
Next, the researchers looked at the nucleolus, which creates protein-assembling structures called ribosomes, was enlarged in the prematurely aging cells compared to healthy cells. Not only that, the team also discovered that the size of the nucleolus also increases in size with age.
This suggests that it may be possible to use the size of the nucleolus as a potential biomarker of aging as well as a possible target for therapies to counter progeria and even regular aging.
Whilst the first part of the experiment showing how one mutation caused a wide change in protein metabolism is intriguing, it was only the case in progeria cells.
The changes to the nucleolus size in both progeria and normal cells is of the most interest here in relation to regular aging. The observation is good news as there is an urgent need for effective aging biomarkers and for academia to reach a consensus on what panel of biomarkers is best to use in the lab for aging research.
The development of accurate and cost-effective biomarkers is something of great interest to the research community and here at LEAF, we are supporting the AgeMeter and MouseAge projects to develop new aging biomarkers.
 Buchwalter. A. & Hetzer. M (2017) Nucleolar expansion and elevated protein translation in premature aging. Nature Communications 8, Article number: 328