Published: Jan. 1, 2024
Language: Английский
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 14, 2025
The hypermetabolic response associated with burns is characterized by skeletal muscle atrophy and an increased incidence of disability death. Significant remodeling the gut microbiota occurs after severe burn trauma. However, specific mechanisms which contribute to burn-induced remain unexplored. results showed that disruption exacerbated atrophy. Fecal metabolite analysis revealed perturbations, primarily within tryptophan (Trp) metabolic pathway. Animal models further demonstrated disorder enhanced expression indoleamine 2,3-dioxygenase 1 (IDO-1) in colon, ultimately resulting Trp depletion kynurenine (Kyn) levels serum muscle. Excessive colonic Kyn released into circulation, transported cells, binds aryl hydrocarbon receptor (AHR), consequently triggering AHR nuclear translocation initiating transcription atrophy-related genes. Notably, samples from patients exhibited depletion, supplementation alleviated rats burns. This study, for first time, demonstrates dysbiosis upregulates IDO-1, promotes Trp-Kyn metabolism, exacerbates atrophy, suggesting may be a potential therapeutic strategy.
Language: Английский
Citations
0
Talanta, Journal Year: 2025, Volume and Issue: 291, P. 127893 - 127893
Published: March 4, 2025
Language: Английский
Citations
0
Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)
Published: March 5, 2025
Aging is associated with a decline in muscle mass and function, increasing the risk of adverse health outcomes. Amino acid profiling has emerged as potential tool for assessing skeletal health. This study examines associations between fasting plasma amino acids, inflammation healthy older young adults. Data from 131 participants (101 adults, 71.5±4.9 years; 30 25.5±3.9 years) were analyzed. Skeletal was assessed using bioimpedance analysis, hand grip strength measured dynamometer. Plasma kynurenine, inflammatory markers (CRP, IL-6) quantified ultraperformance liquid chromatography tandem spectrometry commercial immunosorbent assays, respectively. Older adults exhibited lower levels glutamic acid, isoleucine, leucine, phenylalanine, kynurenine-to-tryptophan (KYN:TRP) ratio compared to younger individuals (all p<0.05). In branched-chain essential acids correlated positively index (SMI) strength, whereas only proline, KYN:TRP showed positive SMI CRP IL-6 several but not individuals. These findings suggest that age-related shifts profiles may reflect underlying changes metabolism highlighting their early indicators decline.
Language: Английский
Citations
0
The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(11), P. 2053 - 2056
Published: May 2, 2023
Due to several advances in medicine over the past 200 years, allied improvements nutrition, sanitation, housing and working conditions, human life expectancy increased dramatically across globe. However, this has not been accompanied by a comparable increase healthspan (considered here as period of free from age-associated disease). As result living longer, greater proportion us will develop age-related chronic diseases (e.g. cardiovascular disease, dementia, type 2 diabetes, sarcopenia), with lifestyle, social psychological factors influencing trajectory disease development severity (Shiels et al., 2019). Notably an estimated two-thirds people 65 years age suffer two or more these diseases, referred multi-morbidities ageing (Figueira 2016). It is well established both model non-organisms that range environmental, pharmacological genetic interventions can extend lifespan preserve physiological function homeostasis old (Gems & Partridge, 2013; Green 2022). A large growing body evidence also establishes physical exercise powerful practice target decrease many mechanisms drive cellular (Carapeto Aguayo-Mazzucato, 2021; Chen Garatachea 2015). Experimental models lifelong establish protection against pro-ageing inflammatory processes, multiple types cancer (Nilsson 2019) signs frailty associated (Garcia-Valles 2013). Importantly, it seems even leisure time activity adopted during mid-life longer (Moore 2012). In special issue The Journal Physiology we are delighted showcase topical reviews research articles followed online symposium, 'Can prevent decline adaptive homeostasis? Evidence organisms tissues', organised Physiological Society on 12 October 2021. This truly multidisciplinary translational, addressing important questions about using molecular, tissue level approaches, humans. authors discuss how deleteriously impacts processes pathways, use other mitigate dyshomeostasis. following pages summarise highlights each papers. first paper issue, 'Drugs, clocks ageing: hype hope, fact fiction', Furrer Handschin show promise modulating process potentially able improve late-life health wellbeing (Furrer Handschin, 2023). Critically, help separate fiction for topic be confusing experts non-experts has, at times, susceptible hyperbole sensationalism. They then compare non-pharmacological interventions, most notably general activity. incredibly timely comprehensive review goes barriers anti-ageing pharmacologics may overcome design realistic effective novel intervention strategies 'Exercise-induced modulation neuroinflammation ageing', Barad, Augusto Kelly disequilibrium within central nervous system (CNS) critical role inter-organ communication play CNS dysfunction, particularly highlighting immune cells (Barad assess showing endurance induce benefits neuroimmune communications ameliorate homeostatic challenges caused immunological stresses ageing. highlight relevance glial metabolic programming different resilience dyshomeostasis exercise. explore potential experimental avenues better understand mechanistic underlying cell function. Finally, concern amongst scientific community, namely limitations disproportionate male animals fundamental biology research. their 'The now: regular maintains vascular women', Tamariz-Ellermann colleagues consider oestrogen plays maintaining females menopause profound (Tamariz-Ellemann wealth demonstrating maintain women, positive effects appear strongly exercise-induced activation oestrogen-related receptor-α. Timing, ever, while initiating around appears preserving than later on, message clear, any stage life-course likely reap multi-systemic benefits. finish note caution, because countries differ significantly participation adherence programmes, there should 'one size fits all' approach when comparing changes demographics. article 'Fasting 20 h does affect increases circulating BDNF humans', Gibbons examine whether brain-derived neurotrophic factor (BDNF) underlies common neuroprotective observed rodents humans intermittent fasting (Gibbons suggest cerebral flexibility (switching glucose ketone bodies/lactate fuel source) induced helps brain limited, but initiates signalling pathways neuronal synaptic plasticity function, such inducing BDNF, thereby helping cognitive Circulating (serum-, platelet- plasma-derived) blood flow (duplex ultrasound) was quantified healthy participants (6 male, 6 female), employing cross-over (1) fasting, (2) light prolonged exercise, (3) short duration, intense (4) combined Surprisingly, did elevate levels despite nine-fold delivery brain. Both irrespective participant fed fasted, levels, being much pronounced high intensity cycling. periodic bouts one feasible avenue boost production slow humans, although imply, required underpinnings. For discussion colleagues' study, including notes clinical implications, see Club Decker (2023). idea white adipose (WAT) acts only relatively inert lipid store confined history, now WAT highly plastic elicits pleiotropic metabolism health. Vasamsetti visceral (VAT) pathology (Vasamsetti 2023) 'Regulation tissue-derived hormones'. Specifically, focus bioactive adipokines, adiponectin omentin, synthesized secreted VAT into circulation acting tissues liver muscle. Some adipokines anti-inflammatory, eliciting beneficial endothelial nitric oxide synthase production, others leptin resistin pro-inflammatory lead dysfunction. change influence parameters inflammation, insulin resistance, profiles significant knowledge gaps actual cytokines particular, they emphasize current difficulties developing therapeutic approaches patients BMI comorbidities syndrome consequently present very cytokine profiles. While have known 100 reduced food intake (caloric restriction) extends delays recently become clear macronutrients micronutrients similarly tour de force, Flores, Lamming 67% essential amino acids histidine, lysine, methionine, phenylalanine, threonine tryptophan individually diet female C57BL/6J mice, examined (Flores showed 12-week exposure diets low threonine, phenylalanine histidine all decreased adiposity energy expenditure relative chow controls, lysine had no effect. went restricting dietary mice obesogenic adiposity, elevated improved number parameters. Indeed, total fat similar maintained weeks. Improvement glycaemic control, enhanced uptake hepatic steatosis were animals, do fibroblast growth 21-dependent. investigated impact initiated 16 month C57BL/6N mice. No effect either sex males. conservation findings correlation between males females. Consequently, work suggests new opportunity worth exploring combat global obesity epidemic. interesting if life-long restriction under chow/obesogenic healthspan. style manuscript Flores colleagues, please enjoy Apolinário, Carneiro Macêdo (Apolinario Mitochondrial dysfunction disruptions protein well-established drivers ageing, contributing musculoskeletal advancing age. pre-clinical trial unique primary osteoarthritis progressively impaired mobility, Musci tested oral phytochemical compound targeting skeletal muscle mitochondrial proteostasis (Musci Treatment compound, called PB125, aspects locomotor respiration. electron transfer capacity, attenuation coupled uncoupled respiration treated supplement. Additionally, synthesis progression attenuated PB125 animals. Treatment-related maintenance voluntary mobility. point out, exciting identify safe supplement, already available improves mobility strength, gait balance. Rahman, Hian-Cheong Thoms, focused work, raise identifying like loss II myofibres, characteristic (Rahman alters metabolites metabolome mediating some adaptations enjoyed youth. 'Exercise aging kynurenine/tryptophan pathway acylcarnitine metabolite pools older adults', Hinkley deep dive metabolome, testing hypothesis response acute blunted adults compared younger (Hinkley carried our profiling phenotyping biopsies obtained young active, active sedentary prior bout report signatures, which involve acylcarnitines. Muscle impacted activity, kynurenine elevations downstream kynurenic acid NAD+ samples regardless Acylcarnitines thought reflect higher concentrations circulation. Here, acylcarnitines exercise-trained adults, finding posit act sink reduce An take-home study variety pools, bodies, among groups studied here, suggesting achieved We grateful speakers who great patience stay encountered pandemic. thank contributors believe produced seminal collection papers exciting, topics homeostasis. Please note: publisher responsible content functionality supporting information supplied authors. Any queries (other missing content) directed corresponding author article. declare competing interests. K.L.H. C.S. contributed conception drafted revised work. read approved final version agree accountable ensuring related accuracy integrity part appropriately resolved. All persons designated qualify authorship, those authorship listed. funding received support bring symposium fruition Caitlin Oates, Events Marketing Officer; Sally Howells, Managing Editor; Diana Jones, Peer Review Manager; peer reviewers manuscripts included issue.
Language: Английский
Citations
2
Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 30, 2024
ABSTRACT Background Although pharmacological effects of SGLT2 inhibitors on the development frailty and sarcopenia were known, role SGLT1 remained less clear. The present study investigated possible effect inhibition these conditions explored potential mediators. Methods A two‐sample Mendelian randomization (MR) analysis was performed to assess index (FI) low grip strength in individuals aged 60 years older using both FNIH EWGSOP criteria. Subsequently, a two‐step MR conducted investigate mediating insulin resistance phenotype identify mediators FI from 1558 plasma proteins 1352 metabolites. Results Genetically predicted associated with decreased ( β : −0.290 [95% CI: −0.399, −0.181]) reduced risk under −0.796 −1.216, −0.376]) criteria −0.287 −0.532, −0.041]). demonstrated SGTL1 alleviating (mediation proportion = 19.56% 8.42%, 30.70%]). After screening, 24 16 metabolites identified as impact FI. Additionally, 13 found mediate according while 22 6 shown Conclusions potentially mitigated through several biological mediators, shedding new light for therapeutic intervention.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Dec. 4, 2023
Abstract Evaluation of the influence primary and secondary aging on manifestation molecular cellular hallmarks is a challenging currently unresolved issue. Our study represents first demonstration distinct role chronic inflammation/physical inactivity – most important drivers aging, in regulation transcriptomic proteomic profiles human skeletal muscle. To achieve this purpose, young healthy people (n=15), (n=8) older (n=37) patients with knee/hip osteoarthritis, model to effect long-term inflammation vastus lateralis muscle, were included study. It was revealed that widespread substantial age-related changes gene expression relative (∼4,000 genes regulating mitochondrial function, proteostasis, cell membrane, secretory immune response) related physical rather than aging. Primary contributed mainly (∼200) encoding nuclear proteins (regulators DNA repair, RNA processing, transcription), (genes respiratory enzymes, complex assembly factors, regulators cristae formation reactive oxygen species production), as well proteostasis. found associated regulated at post-transcriptional level. The set putative their potential transcriptional can be used resource for further targeted studies investigating individual transcription factors emergence senescent phenotype.
Language: Английский
Citations
1
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 19, 2024
Language: Английский
Citations
0
Published: Jan. 1, 2024
Language: Английский
Citations
0