In cell, expanded nucleoli and increased protein synthesis can serve as aging biomarkers, which had been confirmed from patients with Hutchinson-Gilford progeria syndrome (HGPS). This research had published on the Nature Communications at August 30th.
HGPS is a fatal premature aging disorder. Patients with HGPS exhibit features of aging at a young chronological age, including loss of subcutaneous fat and hair, mobility deficits, and arteriosclerosis2. And complications of cardiovascular disease are fatal in the second decade of life. Before the late 20th century, there was very little information about the generation of progeria. In 2003, the progeria was discovered to be caused from a point mutation in position 1824 of the LMNA gene, in which cytosine is replaced with thymine.
Fig.1 Progerin expression drives nucleolar expansion.
However, in the study, researchers investigated protein homeostasis in HGPS, and found a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. Protein turnover is the balance between protein synthesis and protein degradation. Then increased protein synthesis was resulted from the activated nucleoli and enhanced ribosome biogenesis in fibroblasts. Either depleting normal lamin A or inducing mutant lamin A expression would drive nucleolar expansion. Furthermore, there were relevant between nucleolar size and the age of healthy individuals. Ribosomal RNA production could be increased with age. The evidence was indicated that increased nucleolar size and activity could a hallmark of premature aging. This study reported a profound shift in protein metabolism in HGPS and identified nucleolar size and activity as a novel aging biomarker, even regulation of nucleolar activity could be a possible therapeutic target.
Fig.2 Nucleolar size and rRNA production increase during normal aging
Reference
A Buchwalter，MW Hetzer. Nucleolar expansion and elevated protein translation in premature aging. Nature communications, 2017, 8 (1): 328
ASG De, R Bernard, P Cau, et al. Lamin a truncation in Hutchinson–Gilford progeria. Science, 2003, 300 (5628): 2055
