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Muscle atrophy and weakness are among the most detrimental consequences of disuse, microgravity, hospitalisation and ageing. Oxidative modifications of myofibrillar proteins generated by oxidative stress may contribute to the reduced force- and power-generating capacity of skeletal muscles. As part of the 60-day AGBRESA bed rest (BR) study, we studied (1) how microgravity-induced disuse affected markers of systemic and muscle oxidative stress, (2) how these related to muscle function and (3) to what extent artificial gravity (AG) attenuated these changes. Since the myokine irisin may protect against muscle deterioration in disuse, we additionally assessed serum irisin levels. Sixteen men and eight women (33 ± 9 years) participated in the AGBRESA study. Participants were pseudorandomly assigned to a control group (BR only), or a continuous or intermittent centrifugation group (n = 8 in each group) to assess the efficacy of daily 30-min AG in attenuating the adverse effects of BR-induced disuse. Muscle function, muscle protein carbonyls, serum irisin and key modulators of oxidative stress and cell protection in muscle and blood were assessed before, on Day 6, and at the end of BR. BR caused a reduction in peak torque during maximal voluntary isometric knee extension and knee flexion (p < 0.001) that was greater in women than in men (knee extension, w: -39.7 ± 3.5%, m: -25.1 ± 2.4%; knee flexion, w: -32.9 ± 4.5%, m: -10.2 ± 3.5%, p ≤ 0.002) and faster electrically evoked twitch muscle contractions of plantar flexor and knee extensor muscles (half relaxation time and % peak rate of relaxation, p ≤ 0.003). AG attenuated the BR-induced increase in evoked twitch contraction speed in the knee extensors (group × time interactions: half relaxation time, p = 0.009; % peak rate of relaxation, p = 0.030), and the loss of evoked twitch peak torque of plantar flexors (AG - 25%, Controls -48%, group × time interactions, p = 0.020). Neither BR nor AG affected the circulating levels of systemic oxidative stress and muscle carbonyl concentration and serum irisin levels. However, participants with the highest serum irisin and brain-derived neurotrophic factor levels showed lower levels of 8-iso-PGF2α, a marker of systemic oxidative stress (r = -0.486, p = 0.019; r = -0.512, p = 0.012, respectively) and circulating levels of the C-terminal agrin fragment, a biomarker of neuromuscular junction fragmentation. AG exposure attenuated some of the BR-induced changes in twitch contractile properties. Neither BR nor AG induced significant alterations in systemic oxidative stress, or muscle protein carbonylation, suggesting that the main contribution to the BR-induced loss of muscle strength during the AGBRESA study was not oxidative stress. Show less

We examined whether seven consecutive days of warm-water immersion could elevate resting and exercise-induced levels of brain-derived neurotrophic factor (BDNF), irisin and klotho in older adults. These biomarkers support cognitive and metabolic health, but their levels decline with age. Passive heat exposure, like warm-water immersion, may offer a promising alternative to exercise for enhancing cellular-level physiological resilience in populations where exercise is limited. Twelve habitually active older men (median [IQR] age: 68 [64-73] years; Show less

Studies have shown that sarcopenia and its related parameters are associated with cognition. Preclinical evidence suggests that myokines, such as irisin, Brain-Derived Neurotrophic Factor(BDNF), myostatin and Insulin-like Growth Factor-1(IGF-1) might explain this relationship. This study aimed to explore the associations between sarcopenia-related parameters and cognition, and whether myokines influence this association. Exploratory, cross-sectional analysis of data from the Exercise and Nutrition for Healthy AgeiNg (ENHANce,NCT03649698) study. Participants were older adults(≥65 years) with EWGSOP2-defined sarcopenia. Cognitive functioning was assessed by Mini-Mental State Examination(MMSE), Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), Trail Making Test A&B(TMT), Stroop and Maze Test. Sarcopenia-related parameters were measured: Handgrip Strength, Chair Stand Test, appendicular Lean Mass(aLM), Gait Speed (GS) and Short Physical Performance Battery(SPPB). Serum myokines(IGF-1, irisin, myostatin, BDNF) were determined through ELISA. Associations between cognition and sarcopenia-related parameters were analyzed using multivariable regression, adjusting for potential confounders including myokines. Fifty-eight participants were included in this analysis (76.2 ± 6.7 years, ♀:65.5%). After adjustment for age, sex, body mass index, aLM was associated with MMSE(β = 0.193,p = 0.012), RBANS Total(β = 0.196,p = 0.007) and RBANS Attention(β = 0.215,p = 0.002), CST was associated with RBANS Language(β = -0.314,p = 0.030), SPPB was associated with Maze time(β = -0.364,p = 0.004) and TMT-B (β = -0.333,p = 0.013) and GS was associated with TMT-A(β = -0.324,p = 0.045). After adjustments for BDNF& IGF-1, the association between GS and TMT-A became non-significant. Irisin and myostatin did not influence the sarcopenia-cognition associations. Sarcopenia-related parameters are associated with global and specific cognitive domains. BDNF may, partially, explain the association between muscle mass and MMSE. Additional research with larger sample size is needed to confirm these findings. Show less

The muscle-brain axis integrates peripheral metabolic activity with central nervous system function. Among the endocrine signaling molecules regulating such crosstalk, the peptide hormone irisin released during muscle contraction seems to play relevant roles. Irisin is generated by the proteolytic cleavage of the fibronectin type III domain-containing protein 5 and has emerged as a key regulator of neurotrophic and metabolic adaptation. Although initially described as a myokine, irisin is also expressed in adipose and neural tissues, acting through autocrine, paracrine, and endocrine mechanisms. Irisin binds to the αV/β5 integrin receptor complex and activates a network of signaling pathways which promote mitochondrial biogenesis, autophagy, oxidative stress resistance, and modulation of inflammatory responses. Within the central nervous system, irisin induces brain-derived neurotrophic factor expression and contributes to synaptic plasticity, neurogenesis, and cognitive preservation. Experimental models show that irisin reduces amyloid burden, limits α-synuclein pathology, suppresses neuroinflammation, and stabilizes blood-brain barrier integrity, supporting a disease-modifying role in neurodegenerative conditions. In skeletal muscle, irisin stimulates myogenesis, enhances anabolic signaling, and improves metabolic efficiency, suggesting broader relevance for sarcopenia and age-related metabolic decline. Herein, we discuss irisin as a promising biomarker and a candidate therapeutic target for disorders characterized by concurrent muscle deterioration and cognitive impairment. Show less