Aerobic exercise can positively modulate the gut microbiota composition, particularly increasing abundance of SCFA-producing bacteria in in older adults. In a large-scale observational study involving 897 older adults aged over 60 years, Zhu et al. (2020) reported that, compared to sedentary individuals, those who regularly engaged in aerobic physical activity exhibited significantly higher relative abundances of Firmicutes and Verrucomicrobia at the phylum level, and Prevotellaceae and Verrucomicrobiaceae at the family level. These microbiota shifts provide a potential foundation for increased SCFA production. Interestingly, the effects were particularly pronounced in overweight older adults, suggesting that exercise-induced remodeling of the gut microbiota may be especially beneficial for metabolically impaired populations (Zhu et al., 2020). Morita et al. (2019) found that a 12-week aerobic training intervention in healthy older women significantly increased the relative abundance of Bacteroides. In a shorter-term study, Taniguchi et al. (2018) demonstrated that only 5 weeks of moderate-intensity aerobic training significantly increased the fecal abundance of Oscillospira, a known butyrate-producing genus, in older men.

Additionally, some studies have shown that the abundance of SCFA-producing bacteria, such as Bifidobacterium and Lactobacillus, increases with the duration of exercise intervention, indicating a possible time–dose relationship (Hamasaki, 2017; Yang et al., 2021; Bonomini-Gnutzmann et al., 2022). However, it is important to note that excessive or high-intensity exercise may adversely affect the gut microbiota. Overtraining has been associated with a reduction in SCFA-producing bacteria, increased gut permeability, and disruption of mucosal immune homeostasis, potentially triggering systemic inflammation (Yuan et al., 2018). Therefore, in older individuals, moderate-intensity aerobic exercise—such as brisk walking, cycling, or swimming at 50–70% of maximal heart rate for about 30–60 min per session, 3–5 times per week—is generally recommended to optimize gut microbial balance and promote SCFA production while minimizing potential adverse effects (Izquierdo et al., 2021).

Although several studies have demonstrated that aerobic exercise increases the abundance of intestinal SCFA-producing bacteria in older adults, few have directly measured SCFA concentrations in fecal or serum samples. Nonetheless, emerging evidence from both human and animal studies suggests that aerobic exercise may enhance SCFA production by modulating the gut microbiota. For example, Torquati et al. (2023) investigated the effects of an 8-week moderate-intensity aerobic exercise intervention in patients with type 2 diabetes mellitus and reported increased relative abundances of SCFA-producing bacteria such as Bifidobacterium and Akkermansia muciniphila, accompanied by elevated fecal SCFA levels, including acetate, propionate, and butyrate. Consistent with these findings, Matsumoto et al. (2008) showed that 4 weeks of voluntary treadmill running significantly increased cecal butyrate concentrations in rats. These results support the notion that moderate aerobic exercise can promote SCFA production by reshaping gut microbial composition. However, whether similar effects occur in older adults remains unclear. Therefore, further well-designed randomized controlled trials are warranted to elucidate whether aerobic exercise promotes SCFA synthesis through gut microbiota modulation in older adults.

Resistance exercise refers to physical exercise that involves applying external loads (e.g., dumbbells, resistance bands, or machines) to stimulate muscle contraction, thereby enhancing muscle strength and muscle mass. Numerous studies have demonstrated that resistance exercise can increase the cross-sectional area of both type I and type II muscle fibers, promote muscle protein synthesis (MPS), and stimulate muscle hypertrophy (Sayer et al., 2024). Consequently, it has been widely recognized as an effective intervention for the prevention and treatment of sarcopenia in older adults.

However, current evidence regarding the impact of resistance exercise on SCFA levels in older populations remains limited and inconclusive. McKenna et al. (2021) reported that a 10-week resistance exercise program (three sessions per week at 75% 1 repetition maximum) significantly increased the relative abundance of SCFA-producing taxa such as Veillonellaceae and Akkermansia in the gut microbiota of overweight middle-aged and older adults (50–64 years), alongside notable improvements in upper and lower limb muscle strength. In contrast, Agyin-Birikorang et al. (2025) observed that a 10-week resistance exercise intervention (twice weekly at 60% 1 repetition maximum) in previously untrained healthy older individuals (60–80 years) improved skeletal muscle mass but had no significant effects on gut microbial α- or β-diversity, nor did it substantially alter fecal or serum SCFA concentrations. These inconsistencies may stem from differences in baseline gut microbiota composition, dietary control, and variations in training intensity and frequency among study populations (Van Hul and Cani, 2023). Additionally, individual differences in age, metabolic status, and baseline muscle fitness may also affect the effects of resistance exercise on gut microbiota and its metabolites (Wen and Duffy, 2017).

Therefore, the specific effects of resistance exercise on SCFA-producing bacteria and SCFA levels in older adults remain to be fully elucidated. Future studies using standardized protocols, larger sample sizes, and longitudinal designs are needed to determine whether resistance exercise can induce microbial-derived SCFAs production.

Combined exercise, referring to the integration of aerobic and resistance training within a single intervention program, is widely recognized as an effective strategy to synergistically harness the respective benefits of both modalities. By simultaneously improving cardiovascular endurance and increasing muscle strength and mass, combined exercise may provide more comprehensive health benefits, particularly in older adults (Villareal et al., 2017). In recent years, the effects of combined exercise on gut SCFA-producing bacteria and SCFA levels in older adults have attracted growing research interest. Zhong et al. (2021) demonstrated that an 8-week combined exercise intervention significantly increased the relative abundance of SCFA-producing taxa—including Bifidobacteriaceae, Lachnospiraceae, and Mitsuokella—in sedentary older women, while concurrently reducing pro-inflammatory bacteria such as Proteobacteria. Similarly, Erlandson et al. (2021) reported that a 24-week combined exercise program in older adults was associated with increased abundances of Bifidobacterium, Oscillospira, and Anaerostipes, along with elevated fecal butyrate levels. These findings suggest that combined exercise may promote the enrichment of SCFA-producing bacteria in the gut of older adults, thereby increasing SCFA production.

Notably, compared with aerobic or resistance exercise alone, combined exercise appears to be more effective at stimulating SCFA production. For example, Ma et al. (2020) compared the effects of 8-week aerobic, resistance, and combined exercise interventions on serum SCFA levels in db/db mice. They found that although all exercise modalities significantly increased serum SCFA concentrations compared to controls, the combined exercise group showed higher acetate and butyrate levels than the aerobic group, and higher propionate and valerate levels than the resistance group, indicating a superior effect of combined exercise on SCFA production (Ma et al., 2020). The superior SCFA-producing effects of combined exercise may be attributed to the complementary and synergistic physiological mechanisms of the two exercise types. Aerobic exercise primarily enhances gastrointestinal motility and improves mucosal blood flow, thereby creating a gut environment favorable for SCFA-producing anaerobes (Huang et al., 2024). Meanwhile, resistance exercise produces large amounts of lactate through anaerobic glycolysis. Lactate can serve as a substrate for certain gut bacteria (e.g., Veillonella), which convert it into propionate and other SCFAs, further increasing SCFA levels (Zhao et al., 2019; Zhang and Huang, 2023).

In summary, combined exercise, which integrates the advantages of both aerobic and resistance exercise, synergistically promotes the proliferation of SCFA-producing bacteria in the gut and may represent the most effective strategy for enhancing SCFA levels. However, high-quality clinical studies specifically targeting older adults are lacking, and the precise effects of different exercise modalities on SCFA levels in this population remain to be fully elucidated. Future research should also refine parameters such as exercise intensity, frequency, and duration to develop optimized and personalized exercise prescriptions aimed at increasing SCFA levels in older individuals.

Skeletal muscle mass are largely maintained by a dynamic balance between protein synthesis and degradation. Among these processes, the mTORC pathway is a key regulator of muscle protein synthesis. Activation of mTORC1 promotes the phosphorylation of downstream targets such as ribosomal protein S6 kinase (p70S6K) and inhibits eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), thereby facilitating protein synthesis and muscle hypertrophy (Bodine et al., 2001).

Conversely, muscle protein degradation is mainly mediated by two catabolic systems: the ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway. Both are tightly regulated by forkhead box O (FoxO) family transcription factors. Aging is associated with increased inflammation and oxidative stress, leading to reduced protein kinase B (AKT) activity. Reduced AKT signaling promotes the nuclear translocation of dephosphorylated FoxO, which upregulates the expression of key autophagy-related genes (e.g., LC3, Atg4, Beclin1), accelerating protein breakdown and contributing to muscle atrophy (Cui et al., 2020). Additionally, FoxO can activate UPS by inducing the expression of E3 ubiquitin ligases such as muscle ring finger protein-1 (MuRF1) and muscle atrophy F-box protein (Atrogin-1), further promoting muscle protein degradation (Tang et al., 2014).

Evidence suggests that age-related declines in SCFA levels disrupt the anabolic–catabolic balance of muscle protein, favoring increased degradation and reduced synthesis, ultimately leading to sarcopenia (Jiang et al., 2022). However, restoring SCFA levels through dietary strategies or probiotic supplementation reverses these trends, indicating that SCFAs play a crucial role in regulating muscle protein metabolism (Chen et al., 2021; She et al., 2025).

SCFAs exert their effects on protein metabolism mainly through two interrelated mechanisms: activating the mTOR pathway and inhibiting the FoxO-mediated degradation pathway. For example, Mo et al. (2025) found that in mice with sarcopenic obesity induced by a high-fat diet, melatonin supplementation modulated the gut microbiota, promoted SCFA production, and subsequently activated the mTOR/p70S6K signaling pathway, leading to improved muscle mass and strength. Similarly, Liu et al. (2024) reported that exogenous supplementation with SCFAs (acetate, propionate, and butyrate) activated the mTOR/S6K1 pathway in the skeletal muscle of aged SAMP8 mice, alleviating age-related muscle atrophy and functional decline.

In vitro studies further support these findings. SCFAs, particularly butyrate, have been shown to promote myotube growth by inhibiting the FoxO3a/Atrogin-1 pathway and activating the mTOR signaling cascade, thereby reducing muscle protein catabolism and increasing muscle protein synthesis, respectively (Liu et al., 2024). In dexamethasone-induced atrophy models, butyrate decreased the gene expression of Atrogin-1 and MuRF1, and enhanced AKT/mTOR signaling, thereby attenuating muscle atrophy (Zhao et al., 2025). Notably, the protective effects of butyrate were diminished when GPR109A was inhibited using pertussis toxin, indicating that SCFA-mediated muscle protection is at least partially dependent on GPR109A signaling (Zhao et al., 2025).

Beyond direct intracellular signaling, SCFAs also enhance muscle protein anabolism by improving nutrient absorption. Probiotic supplementation following endurance training has been shown to increase the abundance of SCFA-producing bacteria, such as Bacteroides and Prevotella, upregulate intestinal tight junction proteins, and activate gastric protein synthesis pathways (Lamprecht et al., 2012). These changes improve gut barrier integrity, enhance amino acid absorption efficiency, and promote systemic nutrient availability for muscle protein synthesis (Lamprecht et al., 2012). Similarly, a comparative study found that professional rugby players exhibited higher SCFA levels than sedentary controls, which were associated with increased ATP production, enhanced dietary protein utilization, and greater skeletal muscle protein synthesis (Barton et al., 2018). While these observations suggest that microbiota-derived SCFAs may promote muscle protein anabolism by improved nutrient absorption, important limitations remain: SCFAs were not directly measured in the probiotic study, the rugby player study assessed stool rather than circulating levels, and differences in diet quality or protein intake may also explain the associations. Thus, although these studies provide intriguing mechanistic insights, the causal contribution of SCFAs to skeletal muscle anabolism in humans remains to be firmly established and requires trials with direct SCFA measurements and controlled dietary assessments.

In summary, SCFAs may improve muscle protein metabolism and help prevent age-related sarcopenia through multiple mechanisms, including activating anabolic pathways (e.g., mTOR signaling), suppressing catabolic processes (e.g., FoxO signaling), and enhancing nutrient absorption by improving gut barrier function. However, it should be noted that most available evidence derives from studies employing exogenous SCFAs, while human data are limited to indirect associations (e.g., higher dietary fiber intake linked to greater muscle strength) (Otsuka et al., 2023), and no interventional studies have yet directly demonstrated effects on muscle protein turnover. Whether exercise-induced SCFAs exert similar beneficial effects and share the same underlying mechanisms on muscle protein metabolism remains to be fully elucidated and warrants further investigation.

Aging is associated with a chronic, low-grade systemic inflammatory state, known as “inflammaging,” which is characterized by persistently elevated circulating levels of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) (Crunkhorn, 2020). A vicious cycle between augmented pro-inflammatory signaling and cellular senescence further amplifies inflammaging, contributing to the development of several age-related disorders, including sarcopenia (Wang, 2022).

One of the central mechanisms driving inflammaging is gut microbiota dysbiosis (Xu et al., 2024). With advancing age, there is a marked decline in beneficial SCFA-producing bacteria, including Lactobacillus, Bacteroides, and Faecalibacterium prausnitzii, accompanied by an overgrowth of Gram-negative, LPS-producing bacteria (O'Toole and Jeffery, 2015). This microbial shift not only reduces SCFA production but also elevates LPS levels, thereby compromising gut barrier integrity (Yu et al., 2024). Consequently, the reduction in anti-inflammatory capacity, together with increased systemic LPS levels, promotes skeletal muscle inflammation. Indeed, circulating LPS can activate Toll-like receptor 4 (TLR4) on muscle cell membranes, triggering the nuclear factor-kappa B (NF-κB) signaling cascade and promoting the expression of pro-inflammatory cytokines, such as TNF-α and IL-1β (Sailaja et al., 2022). These cytokines impair protein homeostasis by inhibiting the Akt/mTOR signaling pathway, while simultaneously activating catabolic pathways, particularly the UPS and autophagy–lysosome systems, ultimately leading to increased muscle protein degradation and muscle atrophy (Draganidis et al., 2016). Therefore, an inflammatory response induced by SCFA deficiency may represent a key contributing factor in the pathogenesis of sarcopenia.

Emerging evidence suggests that exercise exerts its anti-inflammatory effects, in part, through the modulation of gut microbiota composition and the consequent enhancement of SCFA production. Vijay et al. (2021) reported that a 6-week exercise intervention in community-dwelling older adults significantly increased serum butyrate levels, which were inversely correlated with circulating concentrations of TNF-α and IL-6. Huang et al. (2022) found that 12 weeks of aerobic exercise in apolipoprotein E (APOE) knockout mice markedly increased the fecal abundance of SCFA-producing genera such as Rikenellaceae and Dubosiella, accompanied by elevated SCFA levels and decreased expression of TNF-α and IL-1β.

Mechanistically, SCFAs can directly bind to GPRs on the membranes of immune and epithelial cells or passively diffuse into cells to inhibit histone deacetylases (HDACs) activity, resulting in epigenetic modifications that suppress the NF-κB signaling pathway (Evans et al., 2020). For example, exogenous supplementation with acetate, propionate, and butyrate has been shown to attenuate inflammatory responses by modulating GPR43/HDAC3 signaling and inhibiting the LPS/TLR4/NF-κB pathway in mice with high-fat diet-induced metabolic injury (Wang et al., 2024). Similarly, in LPS-pretreated neutrophils, butyrate and propionate suppress NF-κB activation by inhibiting HDAC activity (Aoyama et al., 2010). Furthermore, Li et al. (2020) reported that in hypercholesterolemic mice, voluntary wheel running not only increased the relative abundances of Lactobacillus and Eubacterium nodatum but also upregulated colonic mRNA expression of GPR109A and GPR41, enhanced SCFA levels (e.g., acetate, propionate, and isobutyrate), and concurrently downregulated inflammatory markers. These findings suggest that exercise-induced SCFAs may exert anti-inflammatory effects through the activation of GPRs and the inhibition of HDACs, thereby suppressing the NF-κB signaling pathway.

Moreover, SCFAs enhance intestinal barrier integrity, thereby indirectly reducing systemic inflammation. Specifically, SCFAs increase transepithelial electrical resistance and upregulate the expression of tight junction proteins such as zonula occludens-1 (ZO-1) and occludin, thereby strengthening gut barrier function (Mann et al., 2024). This prevents the translocation of bacterial toxins (e.g., LPS) into the bloodstream, effectively reducing upstream triggers of skeletal muscle inflammation and ultimately mitigating inflammatory damage (Roy et al., 2025).

In summary, exercise-induced SCFAs may attenuate chronic low-grade systemic inflammation by activating GPRs signaling, inhibiting HDAC activity, strengthening gut barrier integrity, and reducing LPS translocation, thereby collectively suppressing NF-κB signaling pathways. Therefore, in older adults, exercise-induced SCFAs may play a critical role in preventing and managing age-related sarcopenia through anti-inflammaging mechanisms.

The incidence of insulin resistance increases with age (Walker et al., 2021). With advancing age, abnormal accumulation of intermuscular fat and intramyocellular lipid (IMCL), along with elevated levels of pro-inflammatory cytokines, reduces insulin sensitivity in skeletal muscle, liver, and other peripheral tissues (Chee et al., 2016). This decline in insulin responsiveness impairs glucose homeostasis and ultimately leads to systemic insulin resistance. On one hand, insulin resistance downregulates insulin-like growth factor-1 (IGF-1) signaling and inhibits the downstream phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway, resulting in reduced glucose uptake and utilization and consequently diminishing skeletal muscle protein synthesis (Abdul-Ghani and DeFronzo, 2010; Ji et al., 2025). On the other hand, insulin resistance activates the PI3K/Akt/FoxO pathway, thereby upregulating the expression of muscle atrophy-related genes, such as Atrogin-1 and MuRF-1 (Kitajima et al., 2020; Renna et al., 2019). This promotes skeletal muscle protein degradation and ultimately leads to muscle atrophy. Therefore, insulin resistance is considered an important pathogenic mechanism contributing to the development of sarcopenia.

A large body of research has demonstrated that SCFAs are key modulators involved in regulating insulin sensitivity. SCFAs bind to G-protein coupled receptors GPR43 and GPR41 on the membranes of colonic enteroendocrine L cells, stimulating the secretion of peptide YY (PYY), which enhances glucose uptake and utilization in skeletal muscle and adipose tissue (Boey et al., 2006). Further, SCFAs activate GPR43 on colonic cells, promoting the release of glucagon-like peptide-1 (GLP-1) (Kimura et al., 2013). GLP-1 binds to GLP-1 receptors on pancreatic β and δ cells, thereby enhancing insulin secretion, suppressing glucagon secretion, and ultimately maintaining blood glucose homeostasis (Drucker, 2018).

In addition, SCFAs can increase the adenosine monophosphate (AMP) to adenosine triphosphate (ATP) ratio, thereby activating the AMP-activated protein kinase (AMPK) signaling pathway (Tao and Wang, 2025). In skeletal muscle, SCFA-induced AMPK activation has been shown to enhance mitochondrial fatty acid oxidation, increase energy expenditure, and improve insulin sensitivity in mice (Gao et al., 2009). In the liver, AMPK activation suppresses the expression of gluconeogenic enzymes such as glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), thereby inhibiting gluconeogenesis (Canfora et al., 2015). Indeed, dietary acetate supplementation has been shown to upregulate hepatic AMPK expression and downregulate gluconeogenesis-related gene expression in diabetic mice, leading to reduced blood glucose levels (Sakakibara et al., 2006). These findings suggest that SCFAs inhibit hepatic gluconeogenesis and enhance peripheral glucose utilization by activating the AMPK pathway, thereby improving insulin resistance.

Moreover, SCFAs can enhance skeletal muscle insulin sensitivity through epigenetic modifications. HDAC play a crucial role in chromatin structure remodeling and gene expression regulation by deacetylating histones, thus controlling chromatin accessibility and transcriptional activity (Cheng et al., 2024). Chriett et al. (2017) found that in L6 myotubes with palmitate-induced insulin resistance, butyrate increased histone H3 acetylation near the insulin receptor substrate 1 (IRS1) gene promoter, significantly upregulating IRS1 mRNA and protein expression levels. IRS1, a key initiator of insulin signaling, is mainly distributed in peripheral tissues such as skeletal muscle. Upon activation, IRS1 interacts with the p85 regulatory subunit of PI3K, subsequently activating AKT and promoting the translocation of glucose transporter type 4 (GLUT4), ultimately enhancing glucose uptake and utilization in skeletal muscle and adipose tissue (Maarbjerg et al., 2011; Bo et al., 2024). Furthermore, acetate injection in diabetic rats has been shown to significantly increase GLUT4 mRNA and protein expression levels in skeletal muscle (Yamashita et al., 2009).

Collectively, SCFAs play a pivotal role in improving insulin resistance through multiple mechanisms, including activating GPR41/43-mediated intestinal hormone release, enhancing AMPK-mediated metabolic regulation, and modulating epigenetic modifications to upregulate key insulin signaling molecules such as IRS1 and PI3K/AKT/GLUT4. Therefore, exercise-induced increases in SCFA production may help ameliorate age-related insulin resistance, restore muscle protein synthesis, and reduce protein degradation, ultimately preventing or mitigating sarcopenia in older adults.

Mitochondrial function gradually decreases with age (Harrington et al., 2023). Studies have shown that the number of butyrate producing bacteria in the gut of the elderly is significantly reduced, which leads to the decrease of antioxidant capacity, the increase of reactive oxygen species (ROS) level, and the induction of oxidative damage to mitochondrial DNA (mtDNA), ultimately resulting in mitochondrial dysfunction (Pichaud et al., 2019). Additionally, excessive ROS in skeletal muscle not only upregulates the expression of myostatin, Atrogin-1, and MuRF-1, but also modulates key transcription factors such as NF-κB and FoxO (Ferri et al., 2020). These molecular changes activate both the UPS and the autophagy–lysosomal pathway, leading to impaired mitochondrial function, increased apoptosis, and defective autophagy, thereby contributing to skeletal muscle atrophy (Phua et al., 2024; Guo et al., 2023).

In addition, peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α) is a crucial regulator of mitochondrial function. Upon activation by AMPK phosphorylation and silent information regulator 1 (SIRT1) deacetylation, PGC-1α interacts with downstream molecules such as nuclear factor erythroid 2-related factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), promoting mitochondrial biogenesis and maintaining mitochondrial homeostasis (Herzig and Shaw, 2018). However, during aging, the PGC-1α–NRF1–TFAM signaling pathway in skeletal muscle is impaired, resulting in reduced mitochondrial number and function, which subsequently contributes to sarcopenia (Affourtit and Carré, 2024). Therefore, improving mitochondrial function in skeletal muscle help delay the onset and progression of sarcopenia.

It is well established that exercise acts as an effective activator of mitochondrial function. Studies have shown that aerobic exercise upregulates the expression of PGC-1α, AMPK, and SIRT1 in skeletal muscle, thereby activating downstream effectors such as Nrf2 and TFAM (Smith et al., 2023). This cascade promotes mitochondrial biogenesis, enhances oxidative metabolic capacity, and mitigates muscle loss (Gan et al., 2018). Additionally, resistance exercise has been shown to improve mitochondrial function, increase mitochondrial density and enzymatic activity, and consequently enhance muscle mass and strength, thereby delaying age-related muscle atrophy (Lei et al., 2024). Recently, Uchida et al. (2023) reported that endurance exercise selectively modulates the gut microbiota, increases the abundance of SCFA-producing bacteria, and elevates skeletal muscle endurance, citrate synthase activity, and PGC-1α levels. Interestingly, when mice were treated with antibiotics, these exercise-induced mitochondrial adaptations were markedly diminished, suggesting that improvements in mitochondrial function mediated by exercise are closely linked to an increase in SCFA-producing bacteria (Uchida et al., 2023).

In fact, both animal and cell studies have demonstrated that SCFAs are key mediators in regulating skeletal muscle mitochondrial energy metabolism. Walsh et al. (2015) found that butyrate attenuated muscle atrophy in aged mice by inhibiting HDAC expression in skeletal muscle, which led to upregulation of mitochondrial porin and TFAM levels, and enhanced oxidative metabolic capacity. In a high-fat diet-induced obese mouse model, butyrate supplementation significantly increased the expression of PGC-1α and AMPK in skeletal muscle, accompanied by improved mitochondrial function and biogenesis, indicating that butyrate promotes mitochondrial biogenesis via activation of the PGC-1α/AMPK signaling pathway (Hong et al., 2016). Similarly, Maruta et al. (2016) observed in L6 myotubes that acetate treatment induced AMPK phosphorylation and upregulated both gene and protein expression of GLUT4 and myoglobin, thereby improving lipid metabolism in skeletal muscle.

In conclusion, exercise-induced SCFAs may activate the PGC-1α/AMPK/TFAM signaling pathway by inhibiting HDAC activity, thereby improving mitochondrial function in skeletal muscle and ultimately delaying the onset and progression of sarcopenia. However, direct evidence demonstrating that exercise-induced changes in gut microbiota-derived SCFAs improve skeletal muscle mitochondrial function and prevent sarcopenia remains limited. Therefore, further studies are needed to confirm this mechanism.