Biology subjects

Alldritt, I.

Publications and source records attributed to Alldritt, I..

3 recordsLinked to original sources

bioRxiv2026

Ageing blunts the phospho-proteomic response to resistance exercise in humans

Ageing blunts the adaptive growth response in human skeletal muscle. To define the molecular processes underlying this impairment, we performed unbiased analysis of the phosphoproteome and total proteome in healthy young and old human skeletal muscle following acute resistance exercise (ResEX) and essential amino acid (EAA) ingestion. Ageing led to global suppression of the growth-induced global phosphoproteome, despite intact mTORC1 activation in old muscle. Our results identify widespread effects of ageing on skeletal muscle growth and highlight novel pathways for therapeutic development in aged skeletal muscle.

physiology↗

bioRxiv2025

Exercise training improves sarcopenic muscle function via restoration of mitochondrial quality control

Mitophagy is an essential component of the mitochondrial quality control program, maintaining mitochondrial homeostasis in metabolic tissues such as skeletal muscle. With age, it is thought that mitochondrial quality control becomes dysregulated, leading to the progression of age-associated diseases such as sarcopenia. Exercise is known to enhance skeletal muscle mitochondrial health and may be an effective intervention to prevent sarcopenia, however the role of mitophagy in this process is unknown. Utilising mitophagy reporter mice (mito-QC), we assessed adaptations in skeletal muscle mitophagy in response to increased age (3-26 months) and following an 8-week endurance exercise training period. Immunofluorescent imaging revealed that ageing led to an accumulation of mitolysosomes in sarcopenic old mice indicative of increased mitophagy, an adaptive response that was reversed by exercise training. In parallel to reducing age-associated mitophagy, exercise training increased mitochondrial respiratory capacity and improved muscle strength, suggesting that alterations in mitochondrial quality control led to improvements in skeletal muscle function. Exercise-mediated alterations in mitophagy were accompanied by increases in BNIP3, FUNDC1 and BCL2L13 protein content post training. Collectively our data suggests that sarcopenia leads to dysregulation of mitophagy in skeletal muscle. Restoring mitophagy balance with exercise training leads to improvements in mitochondrial respiration and skeletal muscle strength, identifying a novel cellular mechanism to explain the benefits of exercise training in old age.

cell biology↗

bioRxiv2025

Mitochondrial uncoupler BAM15 improves skeletal muscle function and mitochondrial respiration in Sarcopenia

BackgroundAgeing is accompanied by progressive declines in skeletal muscle mass and strength, culminating in sarcopenia, a condition that contributes to frailty, multimorbidity, and mortality. Age-related changes to mitochondria lead to oxidative damage and dysfunction and are proposed to occur early in the trajectory of sarcopenia, supporting the candidacy of mitochondrial-protective therapies. Here, we test the efficacy of mitochondrial uncoupler BAM15 in age-dependent sarcopenic mouse models. MethodsMale and female MitoQC mice aged 24 months received either standard chow or chow supplemented with BAM15 (0.033% mg/g) ad libitum for eight weeks (n=13-14/group). Young (3-month-old) mice served as reference controls (n=8/group). Muscle mitochondrial respiration was assessed in permeabilized fib res, and contractile function was measured in isolated extensor digitorum longus and soleus muscles. Mitophagy was quantified by immunofluorescence confocal microscopy. Data were analyzed using one-or two-way ANOVA followed by Dunnetts or Bonferronis multiple comparison tests. ResultsAged male and female mice exhibited reduced gastrocnemius muscle mass relative to body mass compared with young controls (p<0.05; [~]18% and [~]32% loss, respectively). BAM15 did not alter muscle size but reversed the age-related loss of contractile function in EDL muscles, to that of the young reference controls in both sexes (p<0.05; [~]33% in males, [~]16% in females). In male mice, BAM15 improved mitochondrial efficiency, evidenced by restoration of Complex I-linked respiration and decreased proton leak ([~]52% improvement; p<0.05), and normalized protein levels of oxidative stress marker 4 -HNE, without changes in mitophagy or mitochondrial content. In females, BAM15 did not improve mitochondrial parameters, which may be, in part, due to aged female muscle exhibiting unchanged Complex I leak and 4-HNE protein abundance, alongside lower complex I subunit (NDUFB8) protein abundance. ConclusionsBAM15 improved skeletal muscle mitochondrial efficiency and contractile function in aged male mice, supporting the potential of mitochondrial uncoupling as a therapeutic strategy for sarcopenia.

physiology↗