Are Aminoglycoside Antibiotics TRPing Your Metabolic Switches?

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1273 - 1273

Published: July 29, 2024

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose noteworthy for being essential establishing systemic metabolic balance. TRP respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades consequence often impinge on mitochondrial function biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown block capacity conduct entry into cell response a wide range biophysical nature, including mechanical, electromagnetic, thermal, chemical. Paradoxically, vitro paradigms commonly used understand organismal development may led astray conventional use streptomycin, an AGA, help prevent bacterial contamination. Accordingly, streptomycin has disrupt both vivo myogenesis, as well phenotypic switch white beige thermogenic status. In vivo, TRP-mediated calcium-dependent exercise adaptations importance metabolism. Alternatively, also curb detrimental levels leakage dystrophic through aberrantly gated TRPC1 be involved etiology X-linked muscular dystrophies. susceptible AGA antagonism critically modulating tissues that, if administered behaving animals, translate systemwide disruption. Regenerative medicine clinical communities need made aware this caveat usage seek viable alternatives, contamination or infection paradigms, respectively.

Language: Английский

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Heat exposure promotes sarcopenia via gut microbiota‐derived metabolites

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract The unprecedented rise in global ambient temperatures the last decade has significantly impacted human health, yet how heat exposure affects development of sarcopenia remains enigmatic. Here, we demonstrate that chronic induces skeletal muscle volume loss, leading to strength and functional decline mice. microbiota composition heat‐exposed mice was analyzed using 16S ribosomal DNA analysis. Liquid chromatography‐mass spectrometry (LC–MS) used explore effects on blood metabolome further analyze correlation between metabolism gut microbiota. Transplantation from germ‐free sufficient increase adverse function host. Mechanistically, an untargeted metabolomics strategy, reveal altered due high is associated with elevated serum levels homocitrulline. Homocitrulline causes mitochondrial dysfunction myocytes by exacerbating ferroptosis levels. And Nrf2 activator (Oltipraz) supplementation alleviates atrophy induced exposure. Our findings detrimental provide new strategies for treating sarcopenia.

Language: Английский

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Aging through the lens of mitochondrial DNA mutations and inheritance paradoxes

Biogerontology, Journal Year: 2024, Volume and Issue: 26(1)

Published: Dec. 27, 2024

Language: Английский

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A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 8, 2023

Abstract To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification a previously undescribed polyacetylene contained root carrots ( Daucus carota ), hereafter named isofalcarintriol, which reveal as potent promoter longevity nematode C. elegans . We assign absolute configuration compound (3 S ,8 R ,9 , E )-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop modular asymmetric synthesis route for all -isofalcarintriol stereoisomers. At molecular level, isofalcarintriol affects cellular respiration mammalian cells, mice, interacts with α-subunit mitochondrial ATP synthase to promote biogenesis. Phenotypically, this also results decreased cancer cell growth, well improved motility stress resistance paralleled by reduced protein accumulation nematodal models neurodegeneration. In addition, supplementation both wild-type C57BL/6NRj mice on high-fat diet, aged chow diet glucose metabolism, increased exercise endurance, attenuated parameters frailty at an advanced age. Given these diverse effects health nematodes might become promising mitohormesis-inducing delay, ameliorate, aging-associated diseases humans.

Language: Английский

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Fasting as a precursor to high‐fat diet enhances mitochondrial resilience in Drosophila melanogaster

Insect Science, Journal Year: 2024, Volume and Issue: 31(6), P. 1770 - 1788

Published: March 21, 2024

Abstract Changes in diet type and nutrient availability can impose significant environmental stress on organisms, potentially compromising physiological functions reproductive success. In nature, dramatic fluctuations dietary resources are often observed adjustments to restore cellular homeostasis crucial survive this of stress. study, we exposed male Drosophila melanogaster two modulated treatments: one without a fasting period before exposure high‐fat the other with 24‐h period. We then investigated mitochondrial metabolism molecular responses these treatments. Exposure preceding resulted disrupted respiration, notably at level complex I. On hand, short maintained respiration. Generally, transcript abundance genes associated mitophagy, heat‐shock proteins, biogenesis, sensing pathways increased either slightly or significantly following remained stable when flies were subsequently put diet, whereas drastic decrease almost all abundances was for directly diet. Moreover, enzymatic activities showed less variation after than treatment Overall, our study sheds light mechanistic protective effects prior highlights metabolic flexibility mitochondria response abrupt changes have implication adaptation species their changing environment.

Language: Английский

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