Intramuscular short‐chain acylcarnitines in elderly people are decreased in (pre‐)frail females, but not in males

Abstract

This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre‐)frailty, reduced physical performance, and altered mitochondrial function. We used a cross‐sectional study design with well‐matched fit and (pre‐)frail old males and females, using young males and females as healthy controls. Frailty was assessed according to the Fried criteria and physical performance was determined by 400 m walk test, short physical performance battery and handgrip strength. Muscle and plasma acylcarnitine status, and muscle mitochondrial gene expression was analyzed. Results showed that intramuscular total carnitine levels and short‐chain acylcarnitine levels were lower in (pre‐)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular short‐chain acylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. It is, therefore, concluded that in (pre‐)frail old females, intramuscular total carnitine levels and short‐chain acylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in aging research.

Matrisome, innervation and oxidative metabolism affected in older compared with younger males with similar physical activity

“…Sex is known to be an important effect modifier in age-related mitochondrial decline, 56 and possibly, the ageing trajectory is sex dependent. 18 Furthermore, in accordance with the current study, a lower mitochondrial complex abundance, TFAM expression and PGC1α expression were observed, even when comparing similarly active, trained older and young individuals, 15 likewise suggesting that physical activity alone is not able to completely halt the age-related decline in mitochondrial capacity. Nonetheless, we do show that spending a higher amount of time in was associated with a higher expression of mitochondrial genes and a lower expression of genes involved in catabolic processes.…”

“…The absence of a significant effect might originate from a more heterogenic study populations due to inclusion of individuals of both sexes in a wider age range. Sex is known to be an important effect modifier in age‐related mitochondrial decline, 56 and possibly, the ageing trajectory is sex dependent 18 . Furthermore, in accordance with the current study, a lower mitochondrial complex abundance, TFAM expression and PGC1α expression were observed, even when comparing similarly active, trained older and young individuals, 15 likewise suggesting that physical activity alone is not able to completely halt the age‐related decline in mitochondrial capacity.…”

“… 16 Furthermore, the ageing trajectory is different between males and females, demanding separate studies for each of the sexes. 17 , 18 Gene expression profiles of vastus lateralis biopsies, obtained by RNA sequencing, were compared between the groups, and key results were validated using quantitative polymerase chain reaction (qPCR) and western blot. Our results show that the cell adhesion, the matrisome, innervation, inflammation and oxidative metabolism are the most significantly regulated processes.…”

“…In addition, many studies investigating the effect of age on muscle function employed a wide range of ages for subject recruitment, which further blurs the effect of age because the loss of muscle mass with age is thought not to be linear 16 . Furthermore, the ageing trajectory is different between males and females, demanding separate studies for each of the sexes 17,18 . Gene expression profiles of vastus lateralis biopsies, obtained by RNA sequencing, were compared between the groups, and key results were validated using quantitative polymerase chain reaction (qPCR) and western blot.…”

Predicting the onset of preeclampsia by longitudinal monitoring of metabolic changes throughout pregnancy with Raman spectroscopy

“…Finally, maternal age is inversely correlated to citric acid, which was expected as genes related to energy metabolism, including TCA cycle metabolites, are downregulated in elderly adults. 81 As the pregnancy advances to the final trimester, we find significant correlations among the clinical factors and metabolites, and cross correlation between the two (Figure 5f). Severity of preeclampsia has moderate to strong correlation to multiple metabolites as represented in Figure 5c.…”