Evidence map›Paper›PMID 41239444›Full record

ArticleClinical epigenetics2025

Does polypharmacy affect epigenetic aging in older people? Evidence from a longitudinal epigenome-wide methylation study.

Alessandro Gialluisi, Alfonsina Tirozzi, Simona Costanzo, Danilo Licastro, Augusto Di Castelnuovo, Miriam Shasa Quiccione, Stefania Falciglia, Margherita Degasperi, Teresa Panzera, Sara Magnacca and 7 more

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

17 authors.

Alessandro GialluisiEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy. Alessandro.gialluisi@neuromed.it.
Alfonsina TirozziEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Simona CostanzoEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Danilo LicastroArea Science Park, Trieste, Italy.
Augusto Di CastelnuovoEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Miriam Shasa QuiccioneEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Stefania FalcigliaUOC Governance del Farmaco, Azienda Sanitaria Regionale del Molise -ASREM, Campobasso, Italy.
Margherita DegasperiArea Science Park, Trieste, Italy.
Teresa PanzeraEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Sara MagnaccaEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Mariarosaria PersichilloEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Fabrizia NoroEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Chiara CerlettiEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Maria Benedetta DonatiEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Giovanni de GaetanoEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Licia IacovielloEpidemiology and Prevention Research Unit, IRCCS Neuromed, Pozzilli, Italy.
Moli-sani Study Investigators

Funding

Agenzia Italiana del Farmaco, Ministero della Salute AIFA-2016-02364690Ministero della Salute GR-2021-12375341NextGenerationEU PE0000015
6 · The paper itself

Abstract

backgroundPolypharmacy, defined as taking ≥ 5 different daily medications, is common in older adults and has been linked with neuropsychiatric/neurological and other health conditions. To clarify the potential molecular implications, we tested the hypothesis that polypharmacy may influence DNA methylation (DNAm) patterns in aging, in a longitudinal Italian cohort (N = 1,098; mean (SD) age at recruitment: 58.8 (5.6) years, 51.3% women; median (IQR) follow-up 12.6 (1.1) years).

resultsWe tested associations of polypharmacy with several DNAm aging clocks (Hannum, Horvath, GrimAge, DNAmPhenoAge, DunedinPACE), through linear mixed models incrementally adjusted for age, sex, education, prevalent health conditions and lifestyles, leukocyte counts and residual batch effects. This revealed significant positive associations of GrimAge acceleration and DunedinPACE with the switch to polypharmacy status during follow-up (Beta (SE): 0.024 (0.008) and0.0012 (0.0004)). While the association of GrimAge was driven by a DNAm-based surrogate of tissue inhibitor metalloproteinase 1 (TIMP-1), no significant association was detected for component CpGs of DunedinPACE. When we tested associations of polypharmacy with 668,413 CpGs epigenome-wide, we observed no statistically significant findings (top hit: cg07675998; chr11q13.1; Beta (SE) = 0.009 (0.002); p = 1.5 × 10

conclusionsThese findings suggest an influence of polypharmacy on accelerated epigenetic aging and on altered methylation patterns in the genome, suggesting a potential implication of pathways related to renal tissue development, lipoproteins and cholesterol homeostasis, inflammatory and immune response, in line with previous proteomic analyses of polypharmacy mouse models. These observations also suggest potential targets for mitigating disruptive effects of polypharmacy on elderly health.

Indexed as

AgingDNA MethylationEpigenesis, GeneticPolypharmacyAgedEpigenomeEpigenomicsFemaleGenome-Wide Association StudyHumansItalyLongitudinal StudiesMaleMiddle AgedAgingChronic health conditionsElderlyEpigenetic clocksInflammationNeurodegenerative and neuropsychiatric diseasePolypharmacy

Identifiers

PMID41239444
PMCPMC12619211

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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 OpenQuestion graph.