Aging is one of the global challenges of our time. The search for new anti-aging interventions is also an issue of great actuality. We report on the success of Drosophila melanogaster lifespan extension under the combined influence of dietary restriction, co-administration of berberine, fucoxanthin, and rapamycin, photodeprivation, and low-temperature conditions up to 185 days in w1118 strain and up to 213 days in long-lived E(z)/w mutants. The trade-off was found between longevity and locomotion. The transcriptome analysis showed an impact of epigenetic alterations, lipid metabolism, cellular respiration, nutrient sensing, immune response, and autophagy in the registered effect.

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Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms.

BACKGROUND: ×Sorbaronia mitschurinii (also known as Aronia mitschurinii) is an intergeneric hybrid of×Sorbaronia fallax and Aronia melanocarpa. ×S. mitschurinii berry is a rich source of phytochemicals such as flavonoids and anthocyanins, which have a broad range of health benefits and a great geroprotective potential. OBJECTIVES: The goal of the present study was to investigate the geroprotective effects of Sorbaronia berry ethanolic extract (SBE) in Drosophila melanogaster and whether these effects depend on the concentration of SBE, duration of treatment, age, and sex. METHODS: SBE was used to supplement a diet of Drosophila imagoes throughout life, during 2 weeks after the imago hatching, and from 4 to 6 weeks of age. The relationship between the SBE effects on lifespan, stress resistance and the expression of stress response genes were examined. RESULTS: SBE treatment at 1-2 and 4-6 weeks of life increased the lifespan, while treatment throughout life reduced lifespan. SBE treatment increased Drosophila resistance to oxidative stress and starvation, but not to hyperthermia. A statistically significant effect of SBE treatment on the expression level of per, keap1, hif1, hsp27, hsp68, hsp83, and sirt1 genes in flies of both sexes and on sod1 expression only in female flies was demonstrated. CONCLUSIONS: The observed relationship between SBE concentration and lifespan effects suggests that the life-extending effect of SBE may be associated with the mechanism of hormesis.

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