Evidence mapPaperPMID 42308222Full record

ArticlePloS one2026

REPROGRAM: REsilience PROmotion with GeRoprotectors: AssessMent of biological effect: Rationale and protocol for a trial of biological effect.

Daisy Wilson, Animesh Acharjee, Niharika A Duggal, Jose R Hombrebueno, Simon W Jones, Jonathan W Lewis, João Pedro de Magalhães, Yessica Martinez-Serrato, Ali Mazaheri, Helen M McGettrick and 11 more

Abstract readClinical Trial Protocol
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Daisy WilsonDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0001-7267-9487
Animesh AcharjeeDepartment of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Niharika A DuggalDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Jose R HombrebuenoDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Simon W JonesDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Jonathan W LewisDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
João Pedro de MagalhãesDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Yessica Martinez-SerratoSchool of Psychology, University of Birmingham, Birmingham, United Kingdom.
Ali MazaheriSchool of Psychology, University of Birmingham, Birmingham, United Kingdom.
Helen M McGettrickDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Sudip MondalDepartment of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Amy J NaylorDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Aline NixonDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Thomas NicholsonDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Judith PartridgeDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Thomas PinkneyUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Nicholas J W RattrayInstitute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Claire StevesDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Kristina TomkovaDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Carly WelchDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Thomas JacksonDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.

Funding

the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC)Wellcome Leap Dynamic Resilience Award
6 · The paper itself

Abstract

backgroundAgeing is associated with reduced resilience to physiological stressors such as infection and surgery. This reduced resilience is believed to be underpinned by the hallmarks of ageing, the key biological mechanisms driving the aged phenotype. Geroprotectors are drugs that are proposed to slow down the ageing process and promote longevity and healthspan. Despite this, mechanistic studies in healthy older adults are lacking. METHODS AND ANALYSIS: This trial will test the hypothesis that geroprotectors targeted towards biological mechanisms associated with poor resilience can reverse these pathways within a three-week period. Three geroprotectors with a good safety profile in older adults and evidence of effect on the hallmarks of ageing will be administered to 60 (30 female; 30 male) adults 70 + . Participants will be randomised to one of three arms (Metformin MR 1500 mg, Fisetin 100 mg or Spermidine 15 mg). Participants will be extensively clinically characterised at baseline. Blood, abdominal adipose tissue and stool samples will be taken at baseline and following the three-week intervention. The primary research question will answer whether a three-week course of Metformin, Spermidine, or Fisetin reduce the number of senescent cells as measured by SA-β-GAL in adipose biopsies in healthy older volunteers. Additionally, there will be assessment of the effect of the geroprotectors on other hallmarks of ageing, including autophagy, immunosenescence, chronic inflammation, dysregulated mTOR signalling, epigenetic age, DNA damage, dysregulated metabolism, stem cell exhaustion and microbial composition. ETHICS AND DISSEMINATION: Ethical approval is in place (24/LO/0549). The main trial report and any sub-studies will be published in high impact peer-reviewed gerontology journals, presented at academic conferences and through a series of public engagement events. Participants enrolled in the study will be informed of the results by a written summary.

trial registrationREPROGRAM was registered with ISRCTN on 10/09/24. ISRCTN47919839. Available at https://www.isrctn.com/search?q=47919839.

Indexed as

AgingAgedCellular SenescenceFemaleHumansMaleMetforminRandomized Controlled Trials as TopicMetformin

Identifiers

PMID42308222
PMCPMC13274875

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.