## 4 Discussion
This pathway is maintained by free fatty acids produced through lipolysis, which stimulate the release of the ubiquitin ligases Atrogin-1 and MuRF1 [31]. In the present study, IL-6 levels were significantly reduced in both experimental groups (\(p\) = 0.033, \(p\) = 0.015), suggesting that RT may help reduce chronic inflammation and its negative effects on muscle tissue. Previous research has shown that high-intensity RT (80% 1 RM) further amplifies IGF-1 secretion [32]. Both groups showed increased IGF-1 levels, which is important for muscle repair and hypertrophy, especially in aging. Muscle protein synthesis (MPS) is generally shown to decrease in older adults. [PERSON] et al. [33] performed low-intensity high-repetition (30% of 1 RM, 20 reps) and high-intensity low-repetition (80% of 1 RM, 8 reps) resistance exercise three times per week for eight weeks in older female adults, and they found that only the low-intensity high-repetition group had a significant increase in IGF-1 at postmortem (\(p\) = 0.06), which differs from our study's findings. These conflicting results are thought to have important implications for intensity settings for RT in the elderly: MPS is slowed in the elderly compared to the young, but an acute increase in Akt-mTORC1 signaling increases MPS to prevent skeletal muscle degradation [34]. Therefore, higher volume (6 sets > 3 sets) of RT may increase type II muscle fiber mobilization and restore the MPS response to a more youthful state. High repetitions, such as LI-HR, can induce metabolic stress through sustained contractions, which can stimulate anabolic hormones such as IGF-1 and growth hormone. Therefore, LI-HR can be a relatively efficient alternative for older adults who cannot perform high-intensity RT. SPARC is essential for extracellular matrix remodeling and mitochondrial biogenesis, which are crucial processes for muscle metabolism during aging. SPARC expression is strongly associated with IGF-1. Melbourne [35] reported that myokine, SPARC, and peroxisome proliferatorator-activated receptor \(\gamma\) coactivator-1 alpha expression was induced in myoblasts after 48 h of electrical pulse stimulation, which is a suitable model of exercise in vitro. This suggests that exercise-induced SPARC is crucially involved in muscle integration through extracellular matrix remodeling and mitochondrial biogenesis [36]. Specifically, exercise-induced SPARC has been shown to regulate extracellular matrix remodeling through the integrin-linked kinase, glycogen synthase kinase 3 beta, [37], transforming growth factor beta 1 (TGF \(\beta\)1) and Smad family member 3 (Smad3) pathways [38]. Therefore, the TGF \(\beta\)1-Smad3-atrogin 1 pathway inhibits the degradation of myogenic transcription factors, including MyoD and myogenin, and promotes muscle differentiation [39]. A previous study showed that growth hormone administration to aged mice ameliorated low intramuscular SPARC expression. This can be attributed to growth hormone/IGF-1 strongly inducing SPARC via the PI3K-dependent signaling pathway. Recent studies have demonstrated a strong association between SPARC and IGF-1, indicating its positive impact on muscle metabolism in aging. Previous animal studies indicated that exercise increases hippocampal BDNF expression and neuroregeneration. For example, [PERSON] et al. reported increased BDNF mRNA expression in the hippocampus after 20 days of voluntary wheel running [40], while [PERSON] et al. reported that treadmill running increased BDNF expression in mice, with repeated exercise amplifying this effect [41]. Acute or chronic exercises increase circulating BDNF in humans. Exercise increases BDNF in the periphery, muscle, and brain, and the longer the exercise duration, the greater the increase [42]. Exercise also increases BDNF production in skeletal muscle, particularly in satellite cells, and can cross the blood-brain barrier into the brain [43,44]. To date, increased BDNF has been reported to be a distinct effect of aerobic exercise in relation to other exercise.