Metabolomics profiling reveals novel markers for leukocyte telomere length

Abstract

Leukocyte telomere length (LTL) is considered one of the most predictive markers of biological aging. The aim of this study was to identify novel pathways regulating LTL using a metabolomics approach. To this end, we tested associations between 280 blood metabolites and LTL in 3511 females from TwinsUK and replicated our results in the KORA cohort. We furthermore tested significant metabolites for associations with several aging-related phenotypes, gene expression markers and epigenetic markers to investigate potential underlying pathways. Five metabolites were associated with LTL: Two lysolipids, 1-stearoylglycerophosphoinositol (P=1.6×10−5) and 1-palmitoylglycerophosphoinositol (P=1.6×10−5), were found to be negatively associated with LTL and positively associated with phospholipase A2 expression levels suggesting an involvement of fatty acid metabolism and particularly membrane composition in biological aging. Moreover, two gamma-glutamyl amino acids, gamma-glutamyltyrosine (P=2.5×10−6) and gamma-glutamylphenylalanine (P=1.7×10−5), were negatively correlated with LTL. Both are products of the glutathione cycle and markers for increased oxidative stress. Metabolites were also correlated with functional measures of aging, i.e. higher blood pressure and HDL cholesterol levels and poorer lung, liver and kidney function. Our results suggest an involvement of altered fatty acid metabolism and increased oxidative stress in human biological aging, reflected by LTL and age-related phenotypes of vital organ systems.

Deoxyribonucleic acid telomere length shortening can predict the incidence of non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus

“…Another limitation of the present study was that the telomere length was determined in peripheral blood leukocytes, but not in the liver. However, recent study by Zierer et al 24 suggested that certain metabolites associated with aging and liver function, such as gamma glutamyl amino acids, are correlated with leukocyte telomere length. Our sample size was relatively small.…”

Appearance of Di‐ and Tripeptides in Human Plasma after a Protein Meal Does Not Correlate with PEPT1 Substrate Selectivity

“…It is however not clear to which extent γ‐glutamyl dipeptides are suitable PEPT1 transport substrates. Yet, a variety of γ‐glutamyl‐peptides have been identified recently in biomarker discovery studies, and some of these peptides can be associated with diseases . We here show that uptake from the intestine from dietary sources contributes to the plasma level of these dipeptides.…”

Metabolism of sleep and aging: Bridging the gap using metabolomics

“…We posit that sleep restriction/deprivation leads to a metabolic setting that could resemble aging and may serve as lead to understand the connection of sleep loss and incident neurodegenerative disorders. Comparison of some recent aging metabolomics studies [47][48][49][50][51][52] and sleep metabolomics studies [61] reveals a striking signature of metabolic similarity. We have analyzed recent aging metabolomics literatures ( Fig.…”

“…In addition, histidine and tryptophan were also found to be significantly changing with age [47]. The same cohort samples were used to demonstrate metabolic association of leucocyte telomere length (LTL), a key cellular phenotype of aging [48]. Specifically, 2 lysolipids, 1-stearoylglycerophosphpinositol and 1-palmitoylglycerophosphoinositol were found to be negatively associated to LTL along with two ␥glutamylamino acids (Supplementary information S1) [48].…”

“…The same cohort samples were used to demonstrate metabolic association of leucocyte telomere length (LTL), a key cellular phenotype of aging [48]. Specifically, 2 lysolipids, 1-stearoylglycerophosphpinositol and 1-palmitoylglycerophosphoinositol were found to be negatively associated to LTL along with two ␥glutamylamino acids (Supplementary information S1) [48]. Altered lipid metabolism and its association with LTL is also evident from American Indian population, with 19 metabolites enriched in lipids (glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester, Supplementary information S1), were significantly associated with LTL [49].…”