KYNURENINE PATHWAY INHIBITORS COMBINED WITH NAD+ PRECURSORS INCREASES LONGEVITY GENE EXPRESSION IN DROSOPHILA
Abstract With rates of aging-related functional decline rising, the need for novel intervention strategies to extend lifespan has increased. In humans, the kynurenine pathway (KP) metabolizes tryptophan and produces nicotinamide adenine dinucleotide (NAD+). KP is correlated negatively with longevity...
Uloženo v:
| Vydáno v: | Innovation in aging Ročník 7; číslo Supplement_1; s. 1073 |
|---|---|
| Hlavní autoři: | , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
US
Oxford University Press
21.12.2023
|
| Témata: | |
| ISSN: | 2399-5300, 2399-5300 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Shrnutí: | Abstract
With rates of aging-related functional decline rising, the need for novel intervention strategies to extend lifespan has increased. In humans, the kynurenine pathway (KP) metabolizes tryptophan and produces nicotinamide adenine dinucleotide (NAD+). KP is correlated negatively with longevity and increased KP metabolite concentrations decrease the average and maximum lifespans in flies. However, genetic and pharmacological inhibition of tryptophan metabolism and dietary supplementation of NAD+ precursors increase the average and maximum lifespans in flies. To comprehensively explore the effects of KP manipulation, we fed DGRP_229 Drosophila males diets infused with ⍺-MT (KP inhibitor), nicotinamide (NAM, an NAD+ precursor), or the combination of NAM and ⍺-MT. We found that all treatments resulted in increased average and maximum lifespans, with the combination treatment displaying the greatest increase compared to the control of 30% (P< 0.0001). The combination treatment resulted in an average lifespan increase of 15% in relation to ⍺-MT alone (P< 0.0001) and 18% in comparison to NAM alone (P< 0.0001). To gain more insight into the biological mechanisms through which different treatments affect lifespan, we performed qRT-PCR on 11 longevity genes in Drosophila. We found that the combination treatment significantly increased the expression of gigas (Gig) (P=0.03), which interacts with Tsc1 to control cellular growth by regulating insulin and TOR signaling pathways, and sirtuin 1 (Sirt1) (P=0.03), an NAD+-dependent histone deacetylase. Our results demonstrate that the combined treatment of KP inhibition and NAD+ precursor elicits a transcription response similar to other lifespan-enhancing treatments and could be used as an alternative intervention method. |
|---|---|
| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 |
| ISSN: | 2399-5300 2399-5300 |
| DOI: | 10.1093/geroni/igad104.3448 |