Transcriptome of aging
A universal aging program has been revealed for the first time
An international group of scientists from the USA and Russia has established drugs that can effectively prolong human life. To do this, they identified a universal aging program by analyzing the activity of genes in long-lived and common nematodes with increasing age. The researchers' article was published in Scientific Reports (Tarkhov et al., A universal transcriptomic signature of age reveals the temporal scaling of Caenorhabditis elegans aging trajectories).
The researchers obtained 60 transcriptomes (a collection of RNA molecules formed during the work of genes) of Caenorhabditis elegans nematodes of different ages, including four long-lived mutants. The average life expectancy of the latter is 2.2-9.4 times higher than that of ordinary people. It turned out that with age there are changes in the concentration of various transcripts, called transcriptomic drift, while these changes in different worms had similar signs.
Scientists have suggested that this is due to the existence of an aging program. The main idea was that there should be some one variable characterizing the state of the regulatory network of genes, and at the same time it should determine the biological age.
Transcriptome analysis showed that 71 genes contribute to biological age. This allowed the researchers to determine by chronological age the biological age of each nematode, regardless of its lifespan. In other words, the researchers determined a common indicator of the "criticality" of the regulatory network of genes. Thus, aging is a consequence of internal instability, lack of control over the activity of genes. This helps to determine which interventions will significantly increase life expectancy.
Scientists compared the transcriptomic picture of aging in long-lived and ordinary forms with the schemes of changes in transcripts when exposed to certain drugs. This approach gave a list of drugs whose action causes changes in RNA, the opposite of the aging process. Among them, anisomycin, alsterpaullone, azacitidine and metamizole turned out to be the most promising.
It is known that certain mutations in genes significantly increase the life of worms, for example, a change in the age-1 gene prolongs the life span by almost 10 times. However, blocking of the corresponding RNA transcripts, especially those initiated at a late age, does not lead to the desired effect. This is due to the fact that mutations may change the genetic "tuning" of the whole organism during development, so the aging of mutant forms may occur in a different way and it is not easy to achieve with the help of a therapeutic approach.
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