Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan DOI
Helena M. Cochemé, Eliano dos Santos

Published: Sept. 13, 2024

Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes extend lifespan and improve in animal models. However, drug development translation particularly challenging geroscience. Preclinical studies have survival as major endpoint for screening, which requires years research mammalian Shorter-lived invertebrates exploited accelerate this process. In particular, the fruit fly

Language: Английский

How does a fly die? Insights into ageing from the pathophysiology of Drosophila mortality DOI Creative Commons
Eliano dos Santos, Helena M. Cochemé

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 4003 - 4015

Published: April 20, 2024

The fruit fly Drosophila melanogaster is a common animal model in ageing research. Large populations of flies are used to study the impact genetic, nutritional and pharmacological interventions on survival. However, processes through which die their relative prevalence still comparatively unknown. Understanding causes death an essential dissect lifespan-extending that organism- or disease-specific from those broadly applicable ageing. Here, we review pathophysiological can lead discuss relation

Language: Английский

Citations

3
Reproductive‐Triggered Sterol Competition Exacerbates Age‐Related Intestinal Barrier Damage in Drosophila Females DOI Creative Commons

Guixiang Yu,

Kejin Chen, Mingyao Yang

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

The trade-off between reproduction and lifespan has been documented across a wide array of organisms, ranging from invertebrates to mammals. In malnourishing dietary conditions, inhibition the reproductive processes generally extends females. However, underlying mechanisms through which nutritional competition driven by accelerates aging remain poorly understood. Here, using female Drosophila melanogaster as model, we show that among various conditions lacking specific nutrients, only sterol deficiency significantly exacerbated both incidence severity intestinal barrier deterioration during aging. Sterile mutation specifically ameliorated such damage in sterol-deprived diets, but failed alleviate age-related under other conditions. Additionally, demonstrate extension amelioration, accompanied suppression effect, pharmacological mTOR or Ras-Erk signaling rapamycin trametinib, were modulated cholesterol levels. Our study also identifies morphological changes excreta sensitive biomarker for early dysfunction. Collectively, these results suggest impairment caused reproductive-induced constitutes significant factor limiting nutritionally unbalanced diets. This work elucidates salient aspect complex interplay resource allocation somatic maintenance, thereby enhancing our understanding how diet impacts process.

Language: Английский

Citations

0
Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila DOI Creative Commons
Jinhua Yan,

Chenxi Feng,

H Zhang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 23, 2025

Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading diminished regeneration an increased risk of age-associated diseases. This study investigates effects Dapagliflozin (DAPA), a novel insulin sensitizer SGLT2 inhibitor, on aging ISCs using Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit MAPK signaling pathway, as confirmed by network pharmacology analysis molecular docking experiments. ameliorates ISC aging, improves function (including enhanced fecal excretion, restored barrier integrity acid-base balance), enhances healthspan. These results highlight potential anti-aging therapeutic agent. provides new evidence application treatment.

Language: Английский

Citations

0
Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan DOI
Helena M. Cochemé, Eliano dos Santos

Published: Sept. 13, 2024

Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes extend lifespan and improve in animal models. However, drug development translation particularly challenging geroscience. Preclinical studies have survival as major endpoint for screening, which requires years research mammalian Shorter-lived invertebrates exploited accelerate this process. In particular, the fruit fly

Language: Английский

Citations

0