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Record W4408977958 · doi:10.1016/j.mad.2025.112054

The impact of a selective androgen receptor modulator (RAD140) on frailty and underlying mechanisms in older male and female C57Bl/6 mice

2025· article· en· W4408977958 on OpenAlexafffund
Stefan Heinze-Milne, Susan E. Howlett

Bibliographic record

VenueMechanisms of Ageing and Development · 2025
Typearticle
Languageen
FieldMedicine
TopicHormonal and reproductive studies
Canadian institutionsDalhousie University
FundersCanadian Institutes of Health ResearchDalhousie Medical Research FoundationHeart and Stroke Foundation of Canada
KeywordsAndrogen receptorAndrogenSenescenceGerontologyAgeingEndocrinologyInternal medicineBiologyPsychologyDevelopmental psychologyMedicineProstate cancerHormone

Abstract

fetched live from OpenAlex

BACKGROUND: Androgen receptors (AR) are promising therapeutic targets for mechanisms of aging, including chronic inflammation, lean mass loss, and worsening bone health. We investigated the impact of RAD140, a selective AR modulator that activates ARs, on frailty and underlying mechanisms in older C57BL/6 mice. METHODS: Mice (23.7-25.5 months; N = 21 males; 15 females) received RAD140 (5 mg/kg/day) or placebo (DMSO) daily for 6-weeks. Frailty (clinical and lab-based), body composition, circulating inflammatory markers, grip strength, and genes relating to function/hypertrophy in quadriceps femoris muscles were assessed. RESULTS: Despite no differences in frailty between treatment and control, there were positive effects in male, but not female mice. RAD140 treated male mice had preserved lean mass (p = 0.024) and bone mineral density (p = 0.004) and lower serum interleukin-6 (p = 0.043) versus controls. In contrast, benefits to body composition and inflammatory markers were not seen in females. In either sex, grip strength, fat mass, and skeletal muscle genes were unaffected. CONCLUSION: Six-weeks of RAD140 treatment did not affect frailty in older male or female mice. The beneficial effects in lean mass, bone mineral density, and systemic inflammation warrant longer treatments to explore any positive impact on frailty in males. RAD140 may not be ideal for achieving these in females.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.566
Threshold uncertainty score0.435

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)0.0000.000

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 head0.027
GPT teacher head0.297
Teacher spread0.269 · 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.

The models applied no category: nothing in the taxonomy fit this work.
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
Published2025
Admission routes2
Has abstractyes

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