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Nedachi, T.

Publications and source records attributed to Nedachi, T..

3 recordsLinked to original sources

Electric-field induced sleep promotion and lifespan extension in Gaucher's disease model flies: Association with improving ER stress and autophagy

Gauchers disease (GD), one kind of genetic disease, is characterized by a mutation in metabolic enzyme, glucocerebrosidase (GBA), leading to accumulation of its substrate, glucosylceramide in tissues. We previously discovered that the minos-inserted mutation of the GBA gene in fruit flies, Drosophila melanogaster, reproduced human GD characteristics and can be used as a promising model for molecular mechanisms study. Recently, we reported that extremely low-frequency electric fields (ELF-EFs) promoted sleep and extended the lifespan of normal flies. In this study, GD model flies were exposed to ELF-EFs, and sleep parameters, gene expressions, and longevity were evaluated. The amount of sleep and lifespan increased after EF exposure. Simultaneously, the expression of the endoplasmic reticulum (ER) stress-related gene, PERK and the autophagy-related gene, p62 was elevated. The data suggest that the healthy effects of EFs on GD flies are associated with improved adaptation to cellular stress.

physiology↗

Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes

The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.

cell biology↗

Effects of a 50-Hz electric field on sleep quality and life span mediated by ultraviolet (UV)-A/blue light photoreceptor CRYPTOCHROME in Drosophila melanogaster

Although electric fields (EF) exert beneficial effects on animal wound healing and differentiation, the molecular mechanisms of these effects have remained unclear for years. Therefore, we aimed to elucidate the molecular mechanisms underlying these effects in Drosophila melanogaster as a genetic animal model. The sleep quality of wild-type (WT) flies was improved by exposure to a 50-Hz (35 kv/m) constant electric field during the daytime, but not during the night. This effect was undetectable in Cryptochrome mutant (Cryb) flies. Exposure to a 50-Hz electric field under low nutrient conditions elongated the lifespan of male and female WT flies by ~18%, but not of three diferrent Cry mutants and Cry RNAi strains. Metabolome analysis indicated that the adenosine triphosphate (ATP) content was 5-fold higher in intact WT than Cry gene mutant strains exposed to an electric field. A putative magnetoreceptor protein and UV-A/blue light photoreceptor, CRYPTOCHROME (CRY) is involved in electric field receptors in animals. The present findings constitute hitherto unknown genetic evidence of a CRY-based system that is electric-field sensitive in animals.

physiology↗