Drosophila Gut—A Nexus Between Dietary Restriction and Lifespan

Abstract

Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension.

The Drosophila gut: A gatekeeper and coordinator of organism fitness and physiology

“…This has important consequences for animal health as many studies have demonstrated that gut integrity is an important determinant of organism fitness and lifespan (Chen, Zheng, & Zheng, ; Clark et al, ; Guo, Karpac, Tran, & Jasper, ; Rera et al, ; Salazar et al, ; Wang, Ryoo, Qi, & Jasper, ). It has become increasingly recognized that in addition to age‐related deterioration of gut integrity, environmental factors affecting gut “fitness,” for example, nutrients and pathogenic infections, are strong determinants of longevity (Ayyaz & Jasper, ; Clark & Walker, ; Lian et al, ). The amenability of flies to genetic manipulations combined with the fact that the signals controlling intestinal homeostasis and disease are highly conserved between Drosophila and humans provide a promising framework for modeling age‐associated human intestinal diseases in flies (reviewed in Apidianakis & Rahme, ; Liu et al, ).…”

α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain

“…The first phenotype resembled partially a Notch ( N ) knockdown-like phenotype with a 4.3 and 4.7-fold, respectively, increase in the total numbers of YFP + cells upon additional expression of α-PheRS and α-PheRS Cys , respectively (Fig 2A-C”’, G). The increase of these midgut progenitor cells (ISCs and EBs) could be a consequence of increased proliferation and/or a differentiation problem of ISCs (Lian et al, 2018; Mundorf et al, 2019). Indeed, we also observed an increase in the proportion of EEs from 8% in the control to 12% in the posterior midguts with elevated α-PheRS expression (Fig 2H), indicating that elevated expression of α-PheRS promotes ISC proliferation and EE accumulation.…”

“…The increase of the midgut progenitor cells (ISCs and EBs) could be a consequence of a differentiation problem of ISCs (Lian et al, 2018;Mundorf et al, 2019). Indeed, we also observed a change in the ratio of EEs / ECs from 0.1 in the wild type to 0.8 in the α-PheRS overexpressing midguts, resulting from counting the cell population in wild type (8% EEs, 68% ECs) and α-PheRS overexpressing posterior midguts, which contained 12% EEs and 14% ECs ( Figure 3K,L).…”

Long-lived animals with negligible senescence: clues for ageing research

“…Though life and health spans have been prolonged in many experimental animals, it has been difficult to conduct studies to test if these regimens also prolong life and health span in humans (2). As the main cause of accelerated mammalian ageing is energy excess, caloric restriction without malnutrition is currently the most effective non-genetic intervention to delay ageing phenotypes in a wide range of mammals from flies (3) to primates (4). A problem with this strategy is that caloric restriction may have adverse effects (4) and reduce quality of life in humans.…”