BACKGROUND: In adipose tissue-muscle crosstalk mechanisms, the interaction of adipokines and myokines is known to be critical for maintaining the body's metabolic balance in age-related metabolic disorders. The aim of the study investigate the effects of 12 weeks of aerobic and resistance exercise training on spexin and follistatin and their relationship with each other. METHODS: This study was a multicentre, randomized controlled study conducted at two assisted living facilities with participants aged >= 65. Among the 66 subjects, 33 were allocated to the exercise group (E) and 33 to the control group (C). The exercise group was administered 50 min of exercise by expert physiotherapists 1 day a week for 12 weeks. Participants in the intervention groups performed exercise assignments two extra days a week, tailored to their specific circumstances and supervised by the institution's physiotherapists. Spexin, follistatin and measurements of metabolic syndrome parameters were performed at the beginning and after 12 weeks. RESULTS: The mean age of the 62 participants who completed the study (E n = 31, C n = 31) was 73.25 +/- 6.44 years, and 62.9% were female. While spexin (E 1090.94 +/- 533.66, C 1142.91 +/- 550.68 pg/mL, p > 0.05) and follistatin (E 50.52 +/- 24.35, C 50.00 +/- 23.52 ng/mL, p > 0.05) values were similar in the two groups at baseline, the values of spexin (E 1311.32 +/- 513.66, C 1033.27 +/- 486.48, p < 0.0001; eta2 0.387) and follistatin (E 64.79 +/- 32.35, C 48.16 +/- 26.27, p < 0.0001; eta2 0.267) in the exercise group were higher than in the control group at week 12. At the 12th week, neck circumference (38.32 +/- 3.41, 37.16 +/- 3.15, p = 0.002), waist circumference (102.64 +/- 13.38, 98.54 +/- 14.47, p < 0.0001), hip circumference (105.70 +/- 15.43, 102.93 +/- 13.48, p < 0.0001), body fat mass (22.69 +/- 7.39, 20.45 +/- 6.22, p < 0.0001) and systolic and diastolic blood pressure (137.19 +/- 13.80, 124.9 +/- 15.18, p = 0.0001, 77.38 +/- 12.10, 72.61 +/- 9.26, p = 0.043) decreased, and body muscle mass (46.32 +/- 8.43, 49.03 +/- 8.58, p < 0.0001) increased in the exercise group compared to baseline. A correlation was observed between the change in follistatin level and the change in spexin level (r 0.438, p = 0.001). A negative correlation was found between the amount of decrease in body fat mass and the decrease in spexin level (r -0.380, p = 0.005). A positive correlation was found between the increase in body muscle mass and the increase in spexin and follistatin (r 0.431, p = 0.001; r 0.490, p < 0.0001, respectively). CONCLUSIONS: It was found that spexin, which provides metabolic homeostasis, and follistatin, which expresses the increase in muscle mass, increased with the implementation of a 12-week aerobic and resistance exercise program in elderly individuals, and these increases were found to be associated with each other. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05251597.

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