C Bétry1, E Meugnier2, M Pflieger2, G Grenet3, S Hercberg4, P Galan5, E Kesse-Guyot5, H Vidal2, M Laville2. 1. Inserm U1060, INRA U1397, université de Lyon, laboratoire Carmen, université Claude-Bernard Lyon 1, INSA-Lyon, faculté de médecine Lyon-Sud, 69600 Oullins, France; CRNH-RA, hospices civils de Lyon, 69310 Lyon, France. Electronic address: cecilebetry@yahoo.fr. 2. Inserm U1060, INRA U1397, université de Lyon, laboratoire Carmen, université Claude-Bernard Lyon 1, INSA-Lyon, faculté de médecine Lyon-Sud, 69600 Oullins, France; CRNH-RA, hospices civils de Lyon, 69310 Lyon, France. 3. CRNH-RA, hospices civils de Lyon, 69310 Lyon, France. 4. Inserm (U1153), Inra (U1125), Cnam, université Paris 13, équipe de recherche en épidémiologie nutritionnelle (EREN), centre de recherche en épidémiologie et statistiques Sorbonne Paris Cité, COMUE Sorbonne Paris Cité, 93017 Bobigny, France; Département de santé publique, hôpital Avicenne, 93017 Bobigny, France. 5. Inserm (U1153), Inra (U1125), Cnam, université Paris 13, équipe de recherche en épidémiologie nutritionnelle (EREN), centre de recherche en épidémiologie et statistiques Sorbonne Paris Cité, COMUE Sorbonne Paris Cité, 93017 Bobigny, France.
Abstract
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24.5±2.9kg.m-2) were included in the Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation and insulin sensitivity were determined using the euglycaemic-hyperinsulinaemic clamp and indirect calorimetry techniques. RESULTS: Robust subjects were more insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose during the euglycaemic - hyperinsulinaemic clamp than did frail subjects. At the gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was lower in robust subjects and correlated with CPT1b expression. CONCLUSION: CPT1b overexpression could be helping to maintain metabolic health with increasing age. Thus, it is suggested that targeting CPT1b expression might be an interesting strategy to counteract frailty at an early stage. In addition, future studies should examine the role of sirtuin in CPT1b expression regulation.
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24.5±2.9kg.m-2) were included in the Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation and insulin sensitivity were determined using the euglycaemic-hyperinsulinaemic clamp and indirect calorimetry techniques. RESULTS: Robust subjects were more insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose during the euglycaemic - hyperinsulinaemic clamp than did frail subjects. At the gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was lower in robust subjects and correlated with CPT1b expression. CONCLUSION:CPT1b overexpression could be helping to maintain metabolic health with increasing age. Thus, it is suggested that targeting CPT1b expression might be an interesting strategy to counteract frailty at an early stage. In addition, future studies should examine the role of sirtuin in CPT1b expression regulation.
Authors: Marcel A Vieira-Lara; Marleen B Dommerholt; Wenxuan Zhang; Maaike Blankestijn; Justina C Wolters; Fentaw Abegaz; Albert Gerding; Ydwine T van der Veen; Rachel Thomas; Ronald P van Os; Dirk-Jan Reijngoud; Johan W Jonker; Janine K Kruit; Barbara M Bakker Journal: BMC Biol Date: 2021-07-30 Impact factor: 7.431