Comparative proteomics analysis of dietary restriction in Drosophila

Abstract

To explore the underlying mechanism of dietary restriction (DR) induced lifespan extension in fruit flies at protein level, we performed proteome sequencing in Drosophila at day 7 (young) and day 42 (old) under DR and ad libitum (AL) conditions. A total of 18629 unique peptides were identified in Uniprot, corresponding to 3,662 proteins. Among them, 383 and 409 differentially expressed proteins (DEPs) were identified from comparison between DR vs AL at day 7 and 42, respectively. Bioinformatics analysis revealed that membrane-related processes, post-transcriptional processes, spliceosome and reproduction related processes, were highlighted significantly. In addition, expression of proteins involved in pathways such as spliceosomes, oxidative phosphorylation, lysosomes, ubiquitination, and riboflavin metabolism was relatively higher during DR. A relatively large number of DEPs were found to participate in longevity and age-related disease pathways. We identified 20 proteins that were consistently regulated during DR and some of which are known to be involved in ageing, such as mTORC1, antioxidant, DNA damage repair and autophagy. In the integration analysis, we found 15 genes that were stably regulated by DR at both transcriptional as well as translational levels. Our results provided a useful dataset for further investigations on the mechanism of DR and aging.

Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin

“…Low energy intake was strongly associated with processes involved in RNA metabolism, particularly splicing and the spliceosome. This has been noted recently in standard caloric restriction models in C. elegans (Heintz et al, 2017), D. melanogaster (Gao et al, 2020), mice (Swindell, 2009), and monkeys (Rhoads et al, 2018;Rhoads et al, 2020). In the monkey study it was concluded that upregulation of splicing indicates that alternate transcripts regulate the broad response to energy depletion (Rhoads et al, 2018).…”

“…An association between the spliceosome and caloric restriction has been reported in C. elegans (Heintz et al, 2017), D. melanogaster (Gao et al, 2020) mice (Swindell, 2009) and Rhesus monkeys (Rhoads et al, 2018;Rhoads et al, 2020). In monkeys, caloric restriction was achieved by providing the monkeys with 30% less food than ad libitum-fed monkeys and this led to increased lifespan (Colman et al, 2009).…”

Nutrition, longevity and disease: From molecular mechanisms to interventions

“…Transcriptional analysis identifies phases of response to DR beginning with activation of oxidative metabolism; followed by stress signaling and lipid metabolism; and then autophagy, stress, and the metabolic switch to increased expression of FAO and gluconeogenic genes (Romey-Glu ¨sing et al, 2018). Proteomic analysis of whole flies reveals subtle differences in the response to DR depending on the age of the animals (Gao et al, 2020).…”

Dietary restriction fails to extend life in stressful environments

“…Studies examining the effects of DR on expression of proteins (e.g. Gao et al, 2020), especially if combined with manipulation of ambient temperature, could provide additional clues on how dietary protein requirements for homeostasis and somatic maintenance are altered by thermal stress.…”