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S-klotho, the shed form of α-klotho, is thought to be an ageing suppressor with functions related to the physiology of energy metabolism. However, it remains unknown whether ageing biomarkers such as S-klotho and/or chronological ageing are associated in any way with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise. The present work investigates the association of BMR and fuel oxidation in basal conditions and during exercise, with plasma S-klotho in middle-aged, sedentary adults. BMR was measured by indirect calorimetry in 74 such subjects (53% women; age 53.7±5.1 years) following standard procedures, and their fuel oxidation estimated via stoichiometric equations. The maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax) were determined using a walking graded exercise test. No relationship was seen between BMR and plasma S-klotho (P>0.1), although both basal fat oxidation and MFO showed positive associations with this protein (both P0.1). The present findings suggest that basal fat oxidation and MFO are strongly associated with plasma S-klotho in middle-aged sedentary adults. These results support the idea that metabolic flexibility is a powerful predictor of biological ageing.

S‐klotho, the shed form of α‐klotho, is thought to be an ageing suppressor with functions related to the physiology of energy metabolism. However, it remains unknown whether ageing biomarkers such as S‐klotho and/or chronological ageing are associated in any way with basal metabolic rate (BMR) and fuel oxidation in basal conditions and during exercise. The present work investigates the association of BMR and fuel oxidation in basal conditions and during exercise, with plasma S‐klotho in middle‐aged, sedentary adults. BMR was measured by indirect calorimetry in 74 such subjects (53% women; age 53.7±5.1 years) following standard procedures, and their fuel oxidation estimated via stoichiometric equations. The maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax) were determined using a walking graded exercise test. No relationship was seen between BMR and plasma S‐klotho (P>0.1), although both basal fat oxidation and MFO showed positive associations with this protein (both P0.1). The present findings suggest that basal fat oxidation and MFO are strongly associated with plasma S‐klotho in middle‐aged sedentary adults. These results support the idea that metabolic flexibility is a powerful predictor of biological ageing., The study was supported by the Spanish Ministry of Education (FPU14/04172 and FPU15/03960), by the University of Granada Plan Propio de Investigación 2016 (Excellence actions: Unit of Excellence on Exercise and Health [UCEES]), by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, and the European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR.