Plasma acylcarnitine levels increase with healthy aging

Abstract

Acylcarnitines transport fatty acids into mitochondria and are essential for β-oxidation and energy metabolism. Decreased mitochondrial activity results in increased plasma acylcarnitines, and increased acylcarnitines activate proinflammatory signaling and associate with age-related disease. Changes in acylcarnitines associated with healthy aging, however, are not well characterized. In the present study, we examined the associations of plasma acylcarnitines with age (range: 20-90) in 163 healthy, non-diseased individuals from the predictive medicine research cohort (NCT00336570) and tested for gender-specific differences. The results show that long-chain and very long-chain acylcarnitines increased with age, while many odd-chain acylcarnitines decreased with age. Gender-specific differences were observed for several acylcarnitines, e.g., eicosadienoylcarnitine varied with age in males, and hydroxystearoylcarnitine varied in females. Metabolome-wide association study (MWAS) of age-associated acylcarnitines with all untargeted metabolic features showed little overlap between genders. These results show that plasma concentrations of acylcarnitines vary with age and gender in individuals selected for criteria of health. Whether these variations reflect mitochondrial dysfunction with aging, mitochondrial reprogramming in response to chronic environmental exposures, early pre-disease change, or an adaptive response to healthy aging, is unclear. The results highlight a potential utility for untargeted metabolomics research to elucidate gender-specific mechanisms of aging and age-related disease.

Altered Serum Acylcarnitines Profile after a Prolonged Stay in Intensive Care

“…Second, the studied population was older and consisted of more males than the reference population. Impact of age on carnitine concentrations is controversial [ 28 , 29 ]. Gender has been supposed to influence carnitine concentrations [ 28 ], but no differences in C0 and AC concentrations between males and females were observed in the reference population as in the ICU survivors.…”

Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

“…Metabolomics studies on aging reported increasing circulating concentrations of acylcarnitines, mostly long-chain, with age [ 43 , 44 ], which could reflect loss in mitochondrial function [ 45 ]. In a study [ 46 ] comparing metabolites in serum samples obtained 7 years apart from the same individuals (KORA S4 and KORA F4), acetylcarnitine and several other acylcarnitines increased in the follow-up samples compared with baseline samples.…”

Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights

“…Metabolites were used as dependent variables, while CAD phenotype and confounders served as independent variables. Regressions using acylcarnitines or carnitine as dependent variable were adjusted for the following confounders age ( 53 , 54 ), sex ( 55 ), HbA1c (%) ( 11 , 56 , 57 ), body fat (%) ( 11 , 58 , 59 ), smoking habits ( 60 ), antihypertensive and lipid lowering medication ( 61 – 64 ) as well as fasting and sampling time ( Supplementary Figure 1 ) ( 65 – 67 ). Regressions using BCAAs as dependent variable were adjusted for the following confounders: age, sex ( 67 – 70 ), skeletal muscle mass ( 71 , 72 ), smoking habits ( 60 , 73 ), sampling time and fasting time ( Supplementary Figure 2 ) ( 65 – 67 ).…”