Longevity Briefs: Can The Cell’s Protein Factories Explain Why Some People Live So Long In Good Health?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Global life expectancy is around 72 years, but some individuals live significantly longer. What’s more, these people seem to be resistant to the development of serious age-related diseases like neurodegenerative and cardiovascular disease. Understanding what makes these people different can help us understand what drives ageing and how we might be able to treat it.

Ribosomes are structures within the cell that are responsible for assembling new proteins according to an RNA blueprint, which is a temporary copy of the relevant DNA code for the protein in question. Animals genetically modified to produce new ribosomes more slowly (and therefore, have a slower rate of protein synthesis) appear to age more slowly. Calorie restriction, which is one of the most well studied approaches shown to slow ageing in animals, also reduces the production of new ribosomes. Is there a relationship between ribosome synthesis and ageing in humans?

What did the researchers do: In this study, researchers analysed white blood cells from 193 long-lived Chinese women (aged around 100), as well as 83 female spouses of these long-lived individuals’ children as a comparison (in the region of China in which the study was done, parents usually live with their youngest son, so the long-lived mother and her daughter in-law share similar living conditions. They analysed the transcriptomes of these white blood cell samples – measuring the transcriptome is a way of studying the activity of different genes. They were interested specifically in whether genes relating to ribosome synthesis were differently expressed in long-lived individuals.

Key takeaway(s) from this research: Genes associated with ribosome synthesis, especially the genes encoding proteins used to build the ribosomes themselves, were less active in long-lived individuals. They also identified a gene, called ETS1, which appeared to be at least partly involved in the decreased ribosomal protein synthesis. ETS1 encodes a molecule called a transcription factor, which binds to regions of the DNA and can enhance the activity of genes, in this case the genes encoding ribosome proteins. ETS1 was less active in long-lived individuals, and when researchers tried disabling ETS1 in isolated human cells, they found that this reduced cellular senescence, which is considered to be one of the hallmarks of ageing.

This suggests that the relationship between ribosomes and ageing in animals could extend to humans, though it’s difficult to say exactly what the implications of this study are at this point. While the researchers didn’t find any relationship between age and the expression of most of the studied genes among the children’s spouses, that doesn’t rule out the possibility that healthy ageing could lead to reduced activity of these genes, rather than the other way round. Experiments in animals and isolated human cells suggest that there is a causal link between reduced ribosomal synthesis and healthy ageing, but we can’t yet know if this is true in living humans. The study also looked at gene expression in white blood cells only, so we don’t know if these relationships exist in other cell types as well.