Dietary Glycine Supplementation Extends Lifespan of Genetically Heterogeneous Mice
Notice bibliographique
Résumé
Preliminary experiments suggested lifespan extension by glycine supplementation (GlyS) without the growth inhibition seen with methionine restriction in Fisher 344 rats. This suggested that the benefit GlyS, rather than owing to increased methionine clearance (as was originally envisioned), was attributable to increased levels of glycine itself, acting via the glycine receptor. The glycine receptor is a glycine‐gated chloride channel that is widespread among cell types, including macrophages, and GlyS has been shown by others to exhibit anti‐inflammatory and anti‐cancer properties in several rodent models, and even to reverse Type 2 diabetes in a human trial. GlyS has also recently been found by others to restore the youthful mitochondrial phenotype in senescent cultured human fibroblasts, whose senescence was linked to epigenetic down‐regulation of the principal pathways of endogenous glycine synthesis. The present study set out to replicate the life extension previously observed in rats, in large, reproducible populations of UM‐HET‐3, 4‐way cross mice, in a Phase I Interventions Testing Program (ITP) trial of the National Institute on Aging (NIA). Beginning at 9 months of age, GlyS mice were fed a diet containing 8% glycine (dry weight, compared to the level of 2.3% in the control diet) simultaneously at 3 sites (The Jackson Labs, Bar Harbor, ME; University of Michigan, Ann Arbor, MI; U.T. Health San Antonio, TX), employing approximately 50 each of male and female GlyS and 100 each of male and female controls at each site. Data were compiled after 90% of control mice had died at all 3 sites. Pooling data from all 3 sites (shown in Figure below), median lifespan was increased among GlyS mice by 3.7% among females and 1.3% among males, and the 90 th percentile lifespan was increased by 1.8% among females and 3.6% among males (p = 0.00004 by log‐rank test and p = 0.002 by Wang‐Allison test for pooled males and females at all 3 sites combined). The observed lifespan extension is statistically robust, in that significant log‐rank p‐values were seen for each sex (pooling across site) and for each site (pooling across sexes). The Stage I ITP protocol measures only lifespan, and it is anticipated that Stage II trials will provide the opportunity for biochemical and other cross‐sectional measures to elucidate the mechanism(s) involved in the life extension observed in our system. Support or Funding Information Interventions Testing Program, National Institute on Aging This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».