Abstract
Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.
Highlights
Aging and age-related metabolic disorders, such as obesity, diabetes, and cardiovascular disease (CVD), pose great social and economic burdens worldwide
We reported that leukocyte telomere length at baseline significantly and independently predicts incident diabetes in American Indians [19], lending further support for a strong relationship between biological aging driven by telomere shortening and metabolic dysregulation
Higher levels of 13 metabolites in the species of glycerolphosphoethanolamines (PEs), glycerophospho-choline (PC), bile acids, fatty amides, L-carnitine ester, peptide, and toluene were significantly associated with longer Leukocyte telomere length (LTL), whereas higher levels of glycerolipids, glycerophosphoglycerol, isoprenoids, and steroids were significantly associated with shorter LTL
Summary
Aging and age-related metabolic disorders, such as obesity, diabetes, and cardiovascular disease (CVD), pose great social and economic burdens worldwide. The aging process is characterized by progressive metabolic decline over time, such as metabolic rate decline [1], reduced insulin secretion and β-cell dysfunction [2, 3], as well as glutathione metabolism [4]. Biological pathways known to be involved in aging are implicated in metabolism. Profound metabolic abnormality represents a hallmark of aging [5]. With the current increase in life expectancy and the heavy burden of age-related disorders, there is an urgent need to elucidate metabolic pathways associated with aging and to develop novel metabolic markers and therapeutic targets for early aging and age-related disorders.
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