Signaling pathways of aging
Rapidly dying Dahomey fruit flies eat more and more often than long-lived insects of the Oregon R line
The staff of the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (Pushchino) together with colleagues from several European countries have identified key differences in the physiology of fruit flies with different life spans. It turned out that in short–lived flies, the genes of the TOR signaling pathway (the target of rapamycin) regulating cell growth and division, as well as the signaling system of octopamine, a substance that provokes eating behavior, are more active. The scientific article is published in The Journals of Gerontology Series A (Gubina et al., Essential physiological differences characterize short- and long-lived strains of Drosophila melanogaster – VM).
Aging is a multifactorial process, and an important role in it is undoubtedly played by the body's genes and their activity. To identify differences in the structure and expression of genes in short–lived and long-lived individuals of the same species, organisms of inbred lines are usually used - those in which all individuals have been close relatives to each other for many generations. This almost certainly affects the genetic pattern of their aging. To avoid distortions caused by the use of closely related individuals, the authors of the new study used the so-called outbred lines of flies of the species Drosophila melanogaster. All insects within one such line have the necessary characteristics for scientists, but they are not close relatives. If the same gene variants are found in them at the same time, we can safely say that these genes really play a role in the processes under study (in this case, aging and life expectancy).
In the new work, two outbred drosophila lines were studied – Dahomey and Oregon R. Dahomey females live 74-79 days – less than representatives of their species on average. Females of Oregon R, on the contrary, are long–lived compared to the rest of Drosophila melanogaster - they usually die at the age of 81-86 days. At the beginning of the experiment, all the flies were 10 days old, that is, the insects were quite young and had not yet shown any signs of aging. 20 of them were put in closed vessels without food and water and estimated how many individuals would remain alive 16, 20 and 24 hours after starvation. Another 240 females were killed on purpose, without a period of starvation. Their chest and head were separated from their bodies and the content of various lipids, carbohydrates, proteins and nucleic acids was measured there. Of the latter, RNAs were mainly taken into account: the number of their molecules reflected the activity of the gene from which these RNAs were read.
It turned out that the state of cell membranes and mitochondria, as well as the activity of genes in drosophila organisms of the two lines differ significantly. Intensity of expression of 3,939 genes in fruit flies Dahomey was different from that of the Oregon R. Of these, 1,970 were more active, and 1,969 were weaker than those of Oregon R flies. Among the genes that were particularly strongly expressed were those that enhance the work of the TOR signaling pathway. It stimulates cell division and growth, as well as aging processes. In addition, a greater proportion of lipids were oxidized in the cells of short-lived flies than in long–lived fruit flies - that is, the degree of oxidative stress of their cell membranes was higher. Also, Dahomey cells were found to have an increased content of octopamine, a signaling substance that provokes eating behavior, especially in conditions of lack of food. Finally, flies of the short-lived line died of hunger earlier on average than Oregon R females.
Such results give the right to assert that even young individuals who have not yet begun to age already show features of physiology that allow us to estimate their life expectancy. They also confirm the already known facts that accelerated metabolism and systematic increased food intake bring aging closer. Finally, the work of Russian and foreign biologists has helped to identify specific genes, on the activity of which the life span of "wild type" animals depends – without special DNA modifications and closely related crosses that can distort the picture of the physiology and biochemistry of aging.
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