Polypharmacy, anticholinergic burden and inflammation in relation to accelerated biological ageing

Mar 10, 2026Age and ageing

Multiple medications, drugs that affect the nervous system, and inflammation linked to faster biological aging

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Among 10,556 older adults, 35.0% had polypharmacy and 5.5% had hyperpolypharmacy.

Polypharmacy and anticholinergic burden were significantly linked to accelerated biological ageing, measured by various age indices.
The systemic inflammation response index was found to partially mediate the relationships between polypharmacy and biological ageing.
Mediation analysis indicated that polypharmacy and anticholinergic burden's effects on biological ageing were influenced by inflammation, with specific pathways identified.
Findings highlight the potential role of inflammation in the connection between medication burden and ageing.

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BACKGROUND: Polypharmacy is an emerging public health issue in ageing populations, linked to various adverse outcomes, yet its effect on biological ageing remains unclear. This study investigated the associations of polypharmacy and anticholinergic burden with biological ageing and evaluated the mediating role of systemic inflammation.

METHODS: We analysed data from the cross-sectional National Health and Nutrition Examination Survey (1999-2018), including US adults aged 65 years or older taking at least one prescription medication. Polypharmacy (5-9 drugs) and hyperpolypharmacy (≥10 drugs) were defined by concurrent use. Anticholinergic burden was assessed via the Anticholinergic Drug Scale (ADS). Biological ageing was measured using phenotypic age (PhenoAge), Klemera-Doubal biological age (KD-BioAge), anthropometric age (AnthroAge), frailty index, telomere length and α-Klotho. Inflammation was quantified using five blood cell-based indices. Weighted multiple linear regression and mediation analyses were performed.

RESULTS: Among 10 556 older adults, 35.0% had polypharmacy and 5.5% hyperpolypharmacy. Both polypharmacy and anticholinergic burden were significantly associated with accelerated biological ageing per PhenoAge, KD-BioAge, AnthroAge and frailty index, adjusting for confounders. Systemic inflammation response index (SIRI) partially mediated the associations of polypharmacy and anticholinergic burden with PhenoAge (17.3%-26.9%, both P < .001) and KD-BioAge acceleration (9.8%-11.7%, both P < .001), and the ADS-SIRI pathway serially mediated the associations between polypharmacy and PhenoAge (3.1%, P = .003) or KD-BioAge acceleration (1.7%, P = .005).

CONCLUSIONS: Both polypharmacy and anticholinergic burden are associated with accelerated biological ageing, partly mediated by inflammation, including a potential serial pathway. The findings underscore the importance of deprescribing to reduce ageing-related risks.