Ribosomes in a cell are where proteins are assembled according to a messenger RNA blueprint. Like all cellular components, ribosomes are regularly created and recycled. Reduced production of new ribosomes is a feature of calorie restriction, slowed aging accompanied by a lower output of new proteins. Further, genetic alterations that force a reduction in ribosomal biogenesis also modestly slow aging in animal studies, so it is thought that the pace of protein production is a relevant mechanism in the connection between cellular metabolism and aging. Researchers here extend this line of research into humans, looking at ribosomal function and protein production in long-lived individuals.
As a paradigm of successful human aging, long-lived individuals (LLIs) achieve extreme old age without developing serious age-related diseases (e.g., cardiovascular disease, neurodegenerative disorders, and cancer). Gene expression is thought to have a close association with the activity of processes involved in healthy aging and longevity in LLIs. Here, to find the processes displaying reduced biological activities in long-lived people, we obtained and analyzed the transcriptomes of peripheral white blood cells from 193 female LLIs and 83 gender-matched spouses of LLI children (F1SPs) from two independent Chinese longevity cohorts.
Results showed that genes related to the ribosome pathway, especially ribosomal protein genes (RPGs), were significantly down-regulated in the LLIs. We also found that most of the RPGs were positively coexpressed with the ETS1 gene, which was down-regulated in LLIs. This gene encodes a transcription factor that binds to RPG promoters, and its down-regulation leads to the reduced RPG expression. Furthermore, knockdown of ETS1 alleviated cellular senescence and suppressed RPG transcription in human dermal fibroblast (HDF) and human embryonic lung fibroblast (IMR-90) cells.
Thus, these findings reveal that decreased ribosome biogenesis caused, at least in part, by the down-regulation of ETS1 exists in certain female LLIs and may contribute to healthy aging and life span extension in long-lived people.