Abstracting and Indexing

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Introduction: Polypharmacy is highly prevalent among the elderly and is increasingly recognized as a contributor to adverse health outcomes. Emerging evidence suggests that polypharmacy may induce epigenetic drift, accelerating biological aging and functional decline. However, data from Indian elderly populations are limited. This study aims to investigate the association between polypharmacy-induced epigenetic changes and functional decline in elderly patients at Patna Medical College, India.

Methods: In this cross-sectional study, 250 elderly participants (≥65 years) using ≥5 medications were enrolled. Comprehensive clinical assessments, including the Barthel Index, Clinical Frailty Scale, and MiniMental State Examination (MMSE), were conducted. Peripheral blood samples were analyzed for DNA methylation (using Illumina MethylationEPIC array), histone modifications (via ChIP-seq), and microRNA expression profiles. Drug burden was quantified using the Drug Burden Index (DBI).

Results: Participants had a mean age of 72.8 ± 5.6 years and consumed an average of 7.8 ± 2.1 medications. Higher DBI scores were associated with lower Barthel Index and MMSE scores, indicating greater functional and cognitive impairment. Epigenetic analysis revealed a mean age acceleration of 5.2 ± 2.4 years, with pronounced changes in participants with DBI >2.0. Histone profiling showed reduced H3K4me3 and increased H3K27me3 levels. miR-34a, miR-21, and miR-146a were upregulated, while miR126 was downregulated in high DBI groups.

Conclusion: Polypharmacy is associated with epigenetic drift and accelerated functional decline in Indian elderly. Integrating molecular biomarkers into geriatric care could inform personalized medication management and promote healthy aging.