**Background:** Sarcopenia, the age-related decline in skeletal muscle mass and strength, is a growing public health concern as the global population ages. Muscle atrophy involves degradation of contractile proteins and activation of proteolytic systems, particularly the ubiquitin-proteasome pathway. While turmeric and its bioactive compound curcumin have shown anti-inflammatory and antioxidant properties, their effects on age-related muscle atrophy were not fully understood. This study aimed to investigate the effects of turmeric extract (TE) on age-related skeletal muscle atrophy using a senescence-accelerated mouse model.
**Methods:** Twenty-six-week-old male SAMR (senescence-resistant) and SAMP8 (senescence-prone) mice were divided into three groups (n=7 each): (1) CON group (SAMR mice + normal diet), (2) P8 group (SAMP8 + normal diet), and (3) P8+TE group (SAMP8 + 2% TE-supplemented diet). Mice were housed at 22±1°C, 60±5% humidity, with a 12:12h reversed light/dark cycle and ad libitum access to food and water. After 10 weeks, mice were anesthetized with isoflurane. Lower limb skeletal muscles (gastrocnemius, soleus, plantaris, tibialis anterior, extensor digitorum longus), liver, kidney, and fat tissues (mesenteric, retroperitoneal, epididymal) were removed, weighed, and flash-frozen. Total RNA was extracted from tibialis anterior, gastrocnemius, and soleus muscles using TRIzol reagent and RNeasy Fibrous Tissue Mini Kit. Real-time PCR was performed using Thermal Cycler Dice Real-Time System TP800 with GAPDH as reference. Western blotting was performed on 15-40 µg of protein lysates using antibodies against MAFbx, MuRF1, Rheb, and phosphorylated forms of Akt, mTOR, p70S6K, FoxO1, IRS-1, NF-κB, and IκBα. Statistical analysis used one-way ANOVA followed by Tukey's test with significance at p<0.05.
**Key Results:** No significant differences in weekly mean food intake were observed between P8+TE and P8 groups. Final body weight at week 36 differed between P8+TE and P8 groups. Tibialis anterior muscle weight was significantly different between P8+TE and P8 groups, and between P8+TE and CON groups. Liver weight in the P8 group was significantly different from CON and P8+TE groups. Mesenteric fat tissue showed a trend toward difference between P8 and P8+TE groups (p=0.052). In gastrocnemius and soleus tissues, klf15, redd1, foxo1, mafbx, and murf1 mRNA were downregulated in P8+TE compared to P8. In tibialis anterior, redd1 was significantly downregulated and mfn2 was significantly upregulated in P8+TE vs P8. Foxo1 was significantly downregulated in soleus of P8+TE vs P8 (p<0.05) and showed a trend in gastrocnemius (p=0.056). Tsc2 showed an upregulation trend in tibialis anterior (p=0.09). However, protein expression of MAFbx, MuRF1, and Rheb showed no significant differences between P8 and P8+TE groups. Substrate-level phosphorylation of Akt, mTOR, p70S6K1, 4E-BP1, FoxO1, IRS-1Ser612, IRS-1Ser307, NF-κB, and IκBα in tibialis anterior also showed no significant differences.
**Clinical Implications:** This study provides evidence that TE supplementation may ameliorate age-related muscle atrophy at the transcriptional level by downregulating key genes in the GR-FoxO signaling pathway (klf15, redd1, foxo1, murf1, mafbx) in both fast- and slow-twitch muscles. The significant upregulation of mfn2 suggests TE may also improve age-related mitochondrial dysfunction. The lack of significant protein-level changes may reflect a time lag between mRNA transcription and protein translation. These findings support the potential of TE as a dietary intervention for preventing sarcopenia, particularly relevant for aging societies like Japan. However, the authors acknowledge limitations including the lack of identification of the specific active constituent, absence of metabolomics and metagenomics analyses, and the critical need for human clinical studies to confirm efficacy and determine optimal dosing.