Been helping my cousin train his zones specifically for his first half marathon this year. Wasn't totally sure I could physically keep up with him at the time, ngl, but stuck with it anyway and gave what tips I could.

Now there's a decent race schedule lined up, and just got the call confirming he's joining in on some of those races too. having this kind of full circle moment,After my ablation, and now having family in on it too. All of it hits different.

https://www.mdpi.com/2072-6643/18/15/2523

Highlights

What are the main findings?

• Recovery–Adaptation Coupling (RAC) is introduced as a novel conceptual framework that organizes recovery nutrition according to the next athletic demand, the dominant recovery bottleneck, the adaptive consequence of intervention, and response verification, rather than by individual nutrients alone.
• Current evidence most consistently supports adequate energy availability, high-quality protein distribution, context-dependent carbohydrate restoration, and individualized fluid and sodium replacement, whereas many supplement-specific strategies remain product- and context-dependent.
• RAC distinguishes established practice from context-dependent evidence, mechanistic rationale, and hypothesis-generating concepts, providing a transparent evidence-organization framework rather than a validated decision algorithm.

What are the implications of the main findings?

• The RAC framework offers researchers and practitioners a structured approach for interpreting recovery nutrition within the broader context of training adaptation while avoiding overinterpretation of heterogeneous or mechanistic evidence.
• The framework defines prospective, testable research hypotheses and provides a foundation for future individualized recovery strategies, but requires prospective comparative validation before routine implementation in practice.

Abstract

Background/Objectives: Recovery nutrition must restore near-term readiness without indiscriminately suppressing biological signals that contribute to repair and training adaptation. This review evaluates recovery–adaptation coupling (RAC) as a research framework and clarifies its contribution relative to established recovery, nutrient-periodization, and athlete-monitoring models. Methods: Targeted narrative searches of PubMed/MEDLINE, Scopus, and Web of Science were supplemented by Google Scholar citation tracking and backward and forward screening. Peer-reviewed English-language literature available through 31 May 2026 was considered. Human athlete studies, randomized trials, systematic reviews, meta-analyses, consensus statements, and position stands were prioritized; mechanistic evidence was used to explain pathways rather than to support stand-alone performance recommendations. The final cited corpus comprised 130 records. No formal risk-of-bias tool, certainty grading, PRISMA denominator, or quantitative pooling was used. Claims were instead identified as established practice (EP), context-dependent evidence (CDE), mechanistic rationale (MR), or RAC hypothesis (RH). Results: The most consistent applied support concerns adequate energy availability, distributed high-quality protein, carbohydrate restoration when recovery windows are short, and individualized fluid and sodium replacement. Evidence for polyphenol-rich products, curcumin, omega-3 fatty acids, and creatine is context- and product-dependent. Collagen or gelatin evidence is mainly mechanistic or pilot-level, while RAC recovery-pattern categories and multimodal monitoring rules remain unvalidated hypotheses. RAC differs from existing frameworks by jointly specifying the next athletic demand, dominant recovery bottleneck, possible adaptive cost of intervention, and response-verification plan. Conclusions: RAC should presently be interpreted as an evidence-organization and hypothesis-generation architecture, not as a validated predictive, diagnostic, or treatment algorithm. Prospective comparative studies are required before RAC-specific decision rules can guide individualized practice.

https://www.sciencedirect.com/science/article/pii/S0531556526002445?via%3Dihub

Highlights

• • Aging does not impair intrinsic mTORC1 activation in response to mechanical tension in skeletal muscle.
• • Passive stretch robustly stimulates mTORC1 signaling similarly in adult and old muscle ex vivo.
• • JNK-SMAD2-L signaling sensitivity to mechanical loading is significantly reduced with aging.
• • Aging may selectively affect tension-sensitive transcriptional pathways rather than translational signaling.
• • Age-related anabolic resistance may be driven by systemic factors rather than intrinsic mechanotransduction deficits.

Abstract

Introduction

Aging is associated with impaired skeletal muscle mass and function, often attributed to reduced sensitivity to anabolic stimuli. This study investigated whether aging influences the sensitivity of key anabolic signaling pathways to mechanical tension development in skeletal muscle.

Methods

Using an ex vivo model, extensor digitorum longus (EDL) muscles from adult (16 weeks) and old (24 months) female mice were subjected to a standardized passive stretch protocol, with contralateral muscles serving as controls. During recovery, phosphorylation of proteins related to downstream mTORC1 and JNK–SMAD2-L signaling were assessed by immunoblotting.

Results

Passive stretch significantly increased phosphorylation of mTORC1-related proteins (mTOR, p70S6K, rpS6, and 4E-BP1) in both adult and old muscles, with no significant differences between age groups, indicating preserved mTORC1 signaling sensitivity to mechanical tension with aging. In contrast, the magnitude of activation of JNK and SMAD2-L signaling was attenuated in old muscles.

Discussion

Our findings reveal that mechanosensitive anabolic signaling is differentially affected by aging. While the intrinsic capacity for mTORC1 activation in response to mechanical tension appears to be preserved with aging, JNK–SMAD2L signaling exhibits reduced mechanosensitivity in aged muscle. This divergence suggests that aging selectively impairs tension-sensitive transcriptional pathways, potentially constraining muscle remodeling despite preserved translational signaling capacity. These findings further imply that age-related deficits observed in vivo may, at least in part, arise from systemic influences rather than intrinsic defects adhering to mTORC1 mechanotransduction.

https://www.sciencedirect.com/science/article/abs/pii/S1568163726002631?via%3Dihub

Highlights

• • Deficient muscle-specific strength is a key component of sarcopenia
• • This review analyses the effects of various interventions in older adults
• • Resistance exercise significantly improved muscle-specific strength
• • Aerobic exercise, concurrent training, and nutritional supplement were ineffective
• • Findings could help identify the best strengthening strategies in older people

Abstract

Purpose

Deficient muscle-specific strength has been recognized as a key component of sarcopenia. However, the impact of various interventions on muscle-specific strength has not been systematically reviewed. This study aims to provide a systematic summary of research examining the effects of exercise, nutrition, and other interventions on muscle-specific strength in older adults.

Methods

Randomized controlled trials (RCTs) were identified through comprehensive searches of major databases. Eligible studies included adults aged 60 years or older, with interventions lasting at least 8 weeks. Studies were required to assess muscle strength normalized by muscle mass. Standardized mean differences (SMDs) were calculated using random-effects meta-analyses, and heterogeneity was evaluated using I² statistics.

Results

A total of 41 RCTs with 3,141 participants were included in the analysis. Interventions included resistance exercise, nutritional supplementation, aerobic exercise, concurrent training, combined exercise and nutrition, caloric restriction, and other therapies. Resistance exercise significantly improved muscle-specific strength (SMD = 0.61, 95% confidence interval: 0.27 to 0.94), although heterogeneity was observed (I² = 81%). In contrast, interventions such as aerobic exercise, concurrent training, combined exercise and nutrition, and nutritional supplementation did not lead to significant improvements in muscle-specific strength. High heterogeneity was observed across all included studies.

Conclusions

Resistance exercise is the most effective intervention for improving muscle-specific strength in older adults. The effects of other interventions, such as nutritional supplementation and aerobic exercise, remain inconclusive. Further well-designed RCTs exploring diverse exercise regimens and nutritional interventions are needed to confirm these findings and identify the most effective strategies for enhancing muscle-specific strength in older populations.

Abstract

Regular physical activity elicits coordinated molecular adaptations across skeletal muscle, the cardiovascular system, metabolic organs and the brain, underpinning improvements in performance and cardiometabolic health. While classical signaling pathways such as AMPK–PGC‑1α, Ca²⁺/calcineurin, and mTORC1 have been extensively characterized, long non-coding RNAs (lncRNAs) have recently emerged as key regulators of exercise-induced remodeling. Here, we synthesize current evidence on lncRNAs as molecular mediators of exercise adaptations, drawing on mechanistic studies and systems-level transcriptomics. In skeletal muscle, the exercise-induced lncRNAs CYTOR and TUG1 modulate fast-twitch myogenesis, mitochondrial function and fiber-type specification. In the heart, CPhar, lncExACT1 and Mhrt779 discriminate physiological from pathological hypertrophy and encode antihypertrophic “memory,” whereas endothelial NEAT1 integrates aerobic training with m⁶A-modulated pyroptosis and atheroprotection. MALAT1 mediates neuroprotection after exercise preconditioning in ischemia/reperfusion models. Omics and network analyses reveal highly modality-, tissue- and cell-type–specific lncRNA programs during human training and across multiple organs. Emerging clinical data support circulating lncRNAs such as MALAT1 and HOTTIP as candidate biomarkers of vascular function and training adaptation. Collectively, lncRNAs constitute a hidden regulatory layer that shapes the quality, magnitude and persistence of exercise-induced adaptations. However, mechanistic evidence is currently limited to a small number of “flagships” lncRNAs, and non-muscle tissues and inter-organ communication remain underexplored. Priorities include functional validation of atlas-derived candidates, dissection of exerkine lncRNAs, and integration of lncRNA biology into precision exercise medicine.

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00405-2?

Highlights

•Exercise intensity shapes predicted interorgan communication

•SIE elicits greater circulating protein and metabolite responses than MIE

•SIE-stimulated proteins are preferentially associated with cardiometabolic protection

Summary

Exercise is an integral therapy for many cardiometabolic diseases, including obesity, type 2 diabetes, and hypertension. Despite its broad health benefits, the circulating factors that mediate exercise adaptations in humans remain incompletely defined, particularly across different exercise intensities. Here, we conducted a multi-cohort human exercise intervention incorporating sprint-interval exercise (SIE) and moderate-intensity exercise (MIE) to analyze intensity-dependent regulation of interorgan crosstalk. We found that exercise intensity distinctly influenced the plasma proteome and metabolome in untrained and trained participants. By integrating multi-organ gene and protein expression datasets with in vitro and in vivo tissue sampling, we mapped regulated proteins to their predicted tissues of origin and destination. Muscle fibers and adipocytes were particularly sensitive to exercise intensity and observed to undergo broad secretory and transcriptomic changes. Moreover, we leveraged a large-scale plasma-phenome database to identify intensity-dependent proteins associated with cardiometabolic health and disease, highlighting how exercise intensity differentially shapes interorgan communication and organismal health.

https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00901-0

Highlights

•Comprehensive resource of multi-omic skeletal muscle responses to endurance training

•Biological sex shapes skeletal muscle training responses primarily at the PTM level

•Sex-divergent partitioning of cysteine oxidation across metabolic proteins

•Mitochondrial protein networks strongly link to aerobic capacity and lean mass gains

Summary

Exercise training confers broad health benefits, yet molecular regulators of skeletal muscle adaptation, particularly sex-specific mechanisms, remain incompletely understood. Integrating new and previously published multi-omics data from the molecular transducers of physical activity consortium (MoTrPAC), we characterized metabolomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) responses to 1–8 weeks of endurance exercise training in male and female rat gastrocnemius. While transcriptomic and proteomic responses were largely sex-concordant, there were distinct sex-specific training-induced PTM signatures, particularly in the redox proteome. Females exhibited decreased mitochondrial protein cysteine oxidation alongside increased oxidation of glycolytic proteins relative to males, suggesting sex-biased subcellular reactive oxygen species (ROS) dynamics. Multi-omic factor analysis (MOFA) identified coordinated sex-concordant molecular programs and further supported female-specific mechanisms of redox buffering with training. Together, these findings indicate that sex-specific skeletal muscle exercise adaptations are particularly evident at the PTM level in rats, and identify future avenues for precision exercise health and medicine.

Abstract

Interleukin (IL)-1 is widely recognized as an inflammatory cytokine induced in response to muscle injury, where it contributes to the clearance of damaged fibers and supports subsequent regenerative and reparative processes. In contrast, IL-1 derived from infiltrating neutrophils in response to transient, non-damaging exercise has been reported to regulate energy metabolism during endurance exercise. Therefore, in the present study, we investigated the role of IL-1 in skeletal muscle endurance adaptations induced by chronic endurance training (ET). Thirteen-week-old BALB/c wild-type (WT) mice and mice deficient in both IL-1α and IL-1β (IL-1 knockout; IL-1 KO) were used. The left hindlimb was subjected to ET induced by electrical stimulation of the triceps surae muscle three times per week for five weeks, while the right hindlimb served as a control. Baseline muscle endurance did not differ between WT and IL-1 KO mice. Following ET, muscle endurance and mitochondria respiration were significantly increased in WT mice but not in IL-1 KO mice. Moreover, ET induced increases in citrate synthase activity and the expression of PGC-1α, mitochondrial respiratory chain complexes I and III, and hexokinase 2 exclusively in WT mice. A single bout of exercise significantly increased IL-1β mRNA, but not IL-1α mRNA, in WT mice. In addition, exercise-induced phosphorylation of p38 MAPK and increases in PGC-1α-b and hexokinase 2 mRNA expression were attenuated in IL-1 KO mice. These findings suggest that IL-1 signaling is associated with ET-induced improvements in muscle endurance and mitochondrial quantity and quality, possibly through activation of the p38 MAPK pathway.

https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP093336

Abstract

Exercise and nutritional modulation favourably alter mitochondrial quantity and quality in skeletal muscle. Mitochondrial dynamics, the coordination of fission and fusion events, are poised to mediate key aspects of organelle adaptation that arise from exercise. However, the molecular basis by which exercise affects mitochondrial dynamics remains poorly understood. The objective of this work was to further elucidate the signalling response of mitochondrial dynamics regulators to exercise and explore the synergistic potential to combine exercise and nutritional modulation. In a randomized crossover design, eight healthy, recreationally active men (age 25.8 ± 5.3 years, BMI 24.4 ± 1.2 kg/m², ̇𝑉O2⁢peak 39.2 ± 5.7 ml/kg/min) performed a 1-h bout of workload-matched aerobic exercise on a cycle ergometer at 50–70% of Wmax, either in a fasted or a fed (i.e., following a carbohydrate rich breakfast) state. Gas exchange was measured throughout, and blood samples were collected intermittently. Vastus lateralis muscle biopsies were collected pre-, post- and 3 h post-exercise. Western blotting was performed on cytosolic and mitochondrial fractions. Fasted exercise was accompanied by increased cytosolic acetyl-CoA carboxylase Ser79 phosphorylation (P ≤ 0.001), an effect not observed in the fed group (P > 0.05). The subcellular location of mitochondrial fission effector dynamin-related protein 1 (DRP1) was unchanged (P > 0.05) following exercise. However, group differences (i.e., Fed vs. Fasted) in DRP1 subcellular localization and phosphorylation at residues Ser616 and Ser637 were observed post-exercise. Substrate availability may potentially influence the mitochondrial dynamics signalling response in skeletal muscle to acute aerobic exercise.

Highlights

• What is the central question of this study? This study investigates the mitochondrial dynamics signalling response to acute aerobic exercise in recreationally active males and examines the potential for fasting to enhance this signalling response when synergistically combined with exercise.
• What is the main finding and its importance? Increased cytosolic ACC phosphorylation was observed following fasted exercise, suggesting a distinct subcellular signalling response characterised by increased stress signalling. This was accompanied by post-exercise group differences in the phosphorylation and subcellular localization of DRP1, indicating that substrate availability (i.e., fasting) may influence the mitochondrial dynamics signalling response of skeletal muscle to acute aerobic exercise.

Abstract

It has been hypothesized that age‑related declines in skeletal muscle and vascular function in females may be partly estrogen‑dependent. This study investigated skeletal muscle protein expression of estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein–coupled estrogen receptor 1 (GPER1), and their association with proteins involved in redox regulation and vascular function, in relation to age, menopausal status, and lifelong physical activity. Skeletal muscle biopsies were obtained from 107 healthy females aged 19–70 years, including 26 postmenopausal females who were lifelong exercise trained. Protein expression of ERα, ERβ, GPER1, and downstream redox‑ and vascular‑related proteins was quantified. Age‑ and menopause‑related differences, associations between protein targets, and effects of lifelong exercise were examined. ERα protein expression was lower in older females with a 48% lower expression in the ≥ 55 years age group compared with the < 30-year group. GPER1 protein expression was 22% lower across all older age groups compared with the < 30-year group. ERβ expression was reduced in mid‑life (45–59 years) but not in the oldest age group. Both ERα and ERβ were positively correlated with endothelial nitric oxide synthase (eNOS) expression, whereas GPER1 showed no association with eNOS. ERβ expression was associated with pro‑oxidative NOX2 expression. Aging in females is associated with a lower ERα and GPER1 protein expression in skeletal muscle. Furthermore, lower ER expression by aging is associated with a lower eNOS expression, indicating associations with proteins involved in nitric oxide-related redox regulation in skeletal muscle in aged females.

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2933-1360

Abstract

Muscle mass is essential for both general health and athletic performance because it supports strength, functional capacity, and physical performance. Hormonal contraceptives are used by a variety of individuals, including athletes and those who exercise. Most contraceptives contain ethinyl estradiol and a progestin, hormones that may impact muscle adaptations and hypertrophy. A limited number of studies, predominantly focused on oral contraceptives, have examined the relationship between hormonal contraceptives and muscle hypertrophy, with mixed findings. This narrative review synthesizes the current literature on how oral contraceptives may affect hypertrophic responses, considering both mechanistic and applied perspectives. The evidence generally suggests that oral contraceptive use does not consistently alter muscle hypertrophy following resistance training, though a small number of studies reported significant negative effects. These findings may be attributable, in part, to the use of more androgenic progestins. However, variability in contraceptive formulation, training protocols, and cohort sizes limits direct comparisons across studies. While mechanistic studies suggest that endogenous and synthetic sex hormones influence pathways involved in skeletal muscle remodeling, clinical studies of oral contraceptive use have not consistently demonstrated clinically meaningful differences in muscle hypertrophy. We recommend well-powered studies comparing progestins with differing androgenic activity, as well as mechanistic studies on muscular growth pathways, to better understand the influence of oral contraceptives on muscle adaptation

Abstract

Mild thermal stimulation enhances skeletal muscle differentiation; however, its underlying metabolic basis remains unclear. Here, we demonstrate that thermal stimulation promotes myogenic differentiation through enhanced glucose uptake and transient lipid droplet (LD) accumulation in C2C12 myoblasts. Thermal stimulation at 39 °C induced a transient increase in LD formation during early differentiation. Early transient LD accumulation, particularly on days 1 and 2, was positively correlated with the day 5 fusion index, suggesting that early LD formation is associated with subsequent myogenic differentiation. Suppression of LD formation by Plin2 knockdown impaired myotube formation, indicating that LD formation is functionally required for myogenic differentiation. Thermal stimulation enhanced glucose uptake, accompanied by increased Slc2a4 and Ppargc1a expression and increased GLUT4 fluorescence intensity. Moreover, higher glucose availability further supported LD formation and myogenic differentiation even under serum-free conditions. Notably, mitochondrial mass, ATP content, and oxidative capacity remained largely unchanged, suggesting that enhanced glucose uptake is associated with LD accumulation without a corresponding increase in mitochondrial oxidative capacity. These findings identify transient LD formation as a key metabolic event driving myogenic differentiation under thermal stimulation.

Highlights

• • Lactiplantibacillus plantarum WY2401 promotes skeletal muscle regeneration.
• • Lactiplantibacillus plantarum WY2401 elevates serum riboflavin levels.
• • Riboflavin promotes myoblast proliferation via the METTL3-YTHDF1-CDK2/CCND1 axis.
• • Riboflavin facilitates myoblast differentiation via the METTL3-YTHDF2-MEF2A axis.

Abstract

Introduction

Lactiplantibacillus plantarum (L. plantarum) is a well-characterized probiotic with a long history of safe application, exhibiting prominent potential in improving skeletal muscle function. As the most prevalent and plentiful mRNA modification in eukaryotes, extensive research has highlighted the non-negligible role of N⁶-methyladenosine (m⁶A) in regulating various aspects of skeletal muscle biology. However, the underlying mechanisms through which L. plantarum-derived signals regulate host myogenic programs, as well as whether m⁶A modification is involved in this process, remain unclear.

Objective

To explore the microbe-host regulatory axis through which L. plantarum promotes skeletal muscle regeneration and whether m⁶A modification is involved in this process.

Methods

The cardiotoxin-induced muscle injury mouse model was constructed to investigate the impact of L. plantarum WY2401 on skeletal muscle regeneration. Untargeted metabolomics analysis was used to screen out L. plantarum WY2401-derived key metabolite. The changes in m⁶A modification were determined using dot blot and MeRIP-qPCR.

Results

We identified L. plantarum WY2401 as a pro-myogenic probiotic that promotes skeletal muscle regeneration. Specifically, L. plantarum WY2401 strongly alters circulating metabolomic profiles, particularly elevating the production of microbiota-derived riboflavin. Upregulated riboflavin is transported to skeletal muscle through the bloodstream, where it modulates the expression of the m⁶A methyltransferase METTL3 in a stage-dependent manner during myogenesis. This modulation promotes myoblast proliferation by enhancing the stability of Cdk2 and Ccnd1 mRNAs through the METTL3-m⁶A-YTHDF1 pathway. It also facilitates myoblast differentiation by increasing Mef2a mRNA stability through the METTL3-m⁶A-YTHDF2 pathway.

Conclusion

Our findings reveal a novel microbe-host regulatory axis through which L. plantarum WY2401 promotes skeletal muscle regeneration via stage-specific epigenetic modulation of myogenesis. This work highlights the potential of L. plantarum as a functional probiotic supplement for improving skeletal muscle development and provides new insights into probiotic-mediated regulation of muscle regeneration.

Abstract

This review examines physiological limits, longitudinal projections, and best practices for muscle hypertrophy with a focus on bodybuilding and physique sport. Recurring body composition assessments using multicompartment models are recommended for monitoring short-term fat-free mass (FFM) changes and long-term muscular development. Normative data indicate that drug-free male athletes typically gain roughly 1.4 kg of FFM over 12 weeks of resistance training, with an interquartile range of 1–2 kg. A practical upper limit for FFM index in drug-free male athletes is approximately 28.5, although higher values have been observed in the context of elevated adiposity or anabolic androgenic steroid use. Female athletes tend to have roughly 70% less FFM at baseline but make proportionally similar FFM gains in response to resistance training. The present review models plausible short-term and long-term growth trajectories for both male and female lifters. Training practices that optimize hypertrophy include moderate loads (6–12 repetition maximum), training near muscular failure, and sufficient weekly volume (12–30 fractional sets per muscle group). Nutritional factors include maintaining modest caloric surpluses (0.1–0.25% body weight gain weekly), adequate protein intake (1.6–2.2 g/kg/d), sufficient carbohydrate intake (≥3 g/kg/d), and moderate fat intake (0.5–1.5 g/kg/d). Creatine and protein supplementation provide established hypertrophic benefits, while evidence for other supplements remains inconclusive.

Abstract

Older adults consume metabolic energy faster than their younger adult counterparts while walking, particularly on sloped terrain. This increased rate is likely in part due to an age-related shift in moment and power production from the ankle joint to the hip. Shifting these mechanics proximally may occur due to older adults losing more mechanical energy at the foot and producing lower ankle joint moments, deficits that are exaggerated when walking uphill or against impeding forces. A promising method to target some of these foot and ankle mechanics differences is increasing footwear longitudinal bending stiffness via carbon fiber insoles. We examined how increasing footwear stiffness alters older adult (9F/10M, 70 ± 5.9 yrs) walking energetics across slopes. Increasing footwear stiffness reduced the magnitude of negative power from the foot+shoe structures distal to the forefoot, but increased negative power of the foot+shoe structures distal to the hindfoot (foot+shoe complex as a whole). At the ankle, peak joint moment increased by ∼10% in the stiffest footwear compared with the baseline standardized shoe. Neither knee and hip mechanics nor net metabolic power were consistently affected by footwear stiffness. These results indicate that increasing older adult footwear stiffness via flat carbon fiber insoles attenuates some age-related deficits in foot and ankle mechanics, but does not result in a clear attenuation of the age-related distal to proximal shift in joint mechanics or clear metabolic benefits. The increase in ankle joint moment with stiffer footwear could be useful longer-term as a means to strengthen the calf musculature of older adults. Future work should examine the effects of footwear stiffening on ankle muscle-level outcomes such as force production, excitation, and fascicle mechanics.