The metabolome as a biomarker of aging in Drosophila melanogaster

Abstract

Chronological age is the single greatest risk factor for functional deterioration, chronic diseases, and mortality (Harman, 1991). Several decades of research in laboratory organisms have led to the discovery of numerous hallmarks of aging and of evolutionarily conserved genetic pathways that can extend health span and lifespan (Kaeberlein et al., 2015). However, in real-world settings, individuals vary in genetic and environmental background, and these factors mean that individuals of the same age can differ considerably in patterns of aging, even at quite young age (Belsky et al., 2015). To quantify this variation, to predict future trajectories of aging, and to identify the mechanisms that might underlie this variation, researchers have long sought predictive and prognostic biomarkers of aging (Baker & Sprott, 1988).A diverse array of traits have been identified that associated with chronological age, including morphological and physiological features such as handgrip strength (Bohannon, 2015), vascular structure and function (Fedintsev et al., 2017), facial morphology

Global stable-isotope tracing metabolomics reveals system-wide metabolic alternations in aging Drosophila

“…Drosophila is a widely used model organism to study aging. Previous studies using traditional metabolomics methods have disclosed metabolic changes associated with aging in varied genotypes of Drosophila 35 , 40 , 41 , 43 – 53 (Supplementary Table 7 ). For example, Chang et al 54 , Hoffman et al 45 , and our group 41 reported the declination of metabolites in glycolysis pathway during aging.…”

“…For example, Chang et al 54 , Hoffman et al 45 , and our group 41 reported the declination of metabolites in glycolysis pathway during aging. Metabolites in amino acid metabolism were found to have correlation with aging 46 – 49 , 52 , 53 . For example, Tapia et al revealed that reduction in amino acids such as histidine, tyrosine, and leucine is protective against aging 52 .…”

Metabolome profiling in the study of aging processes

“…наблюдали за когортами из 20 линий дрозофил (англ. Drosophila Genetic Reference Panel, DGRP), выбранных для исследования диапазона вариаций продолжительности жизни, скорости старения и связи этих параметров с возрастными функциональными признаками, включая плодовитость и активность [95]. Несмотря на то, что работа была основана на целевом измерении 87 метаболитов с помощью ЖХ-МС, авторам удалось установить, что уровень активности и профиль метаболома тесно связаны с возрастом, а многие отдельные метаболиты демонстрировали тесную связь с ПЖ.…”

Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

“…L-2HG accumulates in D. melanogaster larvae due to non-canonical activity of dLdh leading to the conversion of αKG to L-2HG [114], or by inhibition the enzyme L-2-hydroxyglutarate dehydrogenase (dL2HGDH) that degrades L-2HG [114]. However, L-2HG levels in D. melanogaster are much lower in adults compared to larvae [114] and a recent study searching for biomarkers of aging in D. melanogaster did not even measure 2HG [115]. To our knowledge, we present here the first demonstration that 2HG increases in the brain of flies with age.…”