Eugenia V. Schegoleva

Cereal grains contain bioactive compounds that may influence longevity. We investigated the effects of 20 cereal varieties on longevity and healthspan in Drosophila melanogaster, including triticale, bread wheat, durum wheats, ancient wheats, and regional varieties. Cereal-based diets exhibited sex-specific differences relative to cereal-free controls: females showed 3–13% longer lifespans while males exhibited reduced lifespans by up to 19%. In females, clear patterns were observed: pronounced lifespan differences (3–11% longer than controls) were concurrent with higher thermotolerance, while moderate lifespan differences (2–6% longer than controls) were associated with greater oxidative stress resistance and locomotor activity, but lower starvation resistance than controls. Males demonstrated higher stress resistance than controls despite shortened lifespan. Gene expression analysis revealed that female-specific lifespan differences were concurrent with elevated expression of immune-related genes (AttA, CecA1, DptA). These results suggest cereal-mediated longevity differences operate through sex-specific physiological pathways involving trade-offs between stress resistance and metabolic regulation.

Small non-coding RNAs coordinate essential cellular processes, including gene expression regulation, genome stability maintenance, and transposon suppression. These processes determine aging, lifespan, and resistance of cells and organisms to stress. In this work, we conducted a comprehensive study of the geroprotective effects of overexpression of two Dicer family genes (Dcr-1 and Dcr-2, which are responsible for the biogenesis of miRNAs and siRNAs) in different tissues of Drosophila melanogaster (nervous system, fat body, intestine, muscles). Activation of the Dicer genes affected the lifespan in a tissue- and sex-depending manner. Females with Dcr-1 overexpression in the nervous system exhibited a significant and reproducible increase in both median (10.0–13.4%, p < 0.001) and maximum lifespan (10.0–13.4%, p < 0.01). However, in other cases, the effect was insignificant or negative. Additionally, flies with neuronal Dcr-1 activation had increased expression of several longevity genes (Sirt1, bsk, tgo, Gadd45, Xpc, Azot, foxo, Hsf, Tsc1) and significantly increased survival after acute exposure to 700 Gy γ-radiation (40–200%, p < 0.05). But they had reduced resistance to starvation. This indicates a crucial role of the miRNA machinery and the Dicer family in providing protection against genotoxic effects and coordinating metabolic processes.

This study investigates how overexpression of circadian clock genes affects longevity and stress resistance in male Drosophila melanogaster. Through analysis of transgenic strains containing UAS-controlled cryptochrome (cry) and period (per) genes with gut-specific GAL4 driver, we demonstrate that circadian gene overexpression produces temporally dependent physiological outcomes. Chronic overexpression throughout lifespan resulted in reduced median lifespan by 9–17% for cryptochrome genes and 4% for period genes (p < 0.05), while transient activation in young-imago ages of cry12, cry24, and per2.4 enhanced thermotolerance, increasing median survival under hyperthermic conditions by 18–25% (p < 0.05). These findings demonstrate that circadian genes act as bidirectional regulators of organismal physiology. The duration of overactivation determines whether the effects are beneficial or detrimental. Future studies are needed to distinguish the effects of stress tolerance from the costs of lifespan in order to enhance stress resistance without compromising longevity.

Endogenous hydrogen sulfide (H₂S) is a gasotransmitter with a wide range of physiological functions. Aging is accompanied by disruption of H₂S homeostasis, therefore, interventions to the processes of H₂S metabolism to maintain its balance may have geroprotective potential. Here we demonstrated the additive geroprotective effect of combined genetic and pharmacological interventions to the hydrogen sulfide biosynthesis system by overexpression of cystathionine-β-synthase and cystathionine-γ-lyase genes and treatment with precursors of H₂S synthesis cysteine (Cys) and N-acetyl-l-cysteine (NAC). The obtained results suggest that additive effects of genetic and pharmacological interventions to H₂S metabolism may be associated with the complex interaction between beneficial action of H₂S production and prevention of adverse effects of excess H₂S production by Cys and NAC treatment.

Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.

Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elements and processes on all levels. Aging Chart (http://agingchart.org/) is a new, community-curated collection of aging pathways and knowledge that provides a platform for rapid exploratory analysis. Building on an initial content base constructed by a team of experts from peer-reviewed literature, users can integrate new data into biological pathway diagrams for a visible, intuitive, top-down framework of aging processes that fosters knowledge-building and collaboration. As the body of knowledge in aging research is rapidly increasing, an open visual encyclopedia of aging processes will be useful to both the new entrants and experts in the field.