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Dietary Glycine Supplementation Extends Lifespan of Genetically Heterogeneous Mice

2018· article· en· W2939645851 on OpenAlexaff
Joel Brind, Richard A. Miller, Randy Strong, David E. Harrison, Francesca Macchiarini

Bibliographic record

VenueThe FASEB Journal · 2018
Typearticle
Languageen
FieldMedicine
TopicBiochemical effects in animals
Canadian institutionsInstitute of Aging
FundersNational Institute on Aging
KeywordsGlycineMethionineSenescenceEndogenyBiologyEndocrinologyEpigeneticsInternal medicineAmino acidMedicineBiochemistryGene

Abstract

fetched live from OpenAlex

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 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.309
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2018
Admission routes1
Has abstractyes

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