Chronic polypharmacy, monotherapy, and deprescribing: Understanding complex effects on the hepatic proteome of aging mice DOI Creative Commons
Kevin Winardi, J.-P. Mach, Matthew J. McKay

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Polypharmacy (use of ≥5 concurrent medications) is highly prevalent among older adults to manage chronic diseases and linked adverse geriatric outcomes, including physical cognitive functional impairments, falls, frailty, hospitalization, mortality. Deprescribing (withdrawal) a potential strategy polypharmacy. The broad molecular changes by which polypharmacy causes harm deprescribing may be beneficial are unknown unfeasible study rigorously in tissue from patients. Therefore, randomized controlled trial, we administered therapeutic doses commonly used medications (oxycodone, oxybutynin, citalopram, simvastatin, or metoprolol) as monotherapy concurrently (polypharmacy) middle-age (12 months) old-age (26 male C57BL/6J (B6) mice deprescribed (gradually withdrew) treatments subset age 21 months. We compared drug-related hepatic effects applying proteomics along with transcriptomics histology. found that on were limited but significant seen (93% unique polypharmacy). altered the expression proteins involved immunity, drug, cholesterol, amino acid metabolism, accompanied higher serum drug levels than monotherapies. not only reversed some also caused irreversible novel proteome. Furthermore, our identified several protein co-expressed modules associated clinically relevant such mobility, activities daily living. This highlights complex following aging, polypharmacy, deprescribing. Further exploration these mechanistic pathways inform management adults.

Language: Английский

Chronic polypharmacy, monotherapy, and deprescribing: Understanding complex effects on the hepatic proteome of aging mice DOI Creative Commons
Kevin Winardi, J.-P. Mach, Matthew J. McKay

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Polypharmacy (use of ≥5 concurrent medications) is highly prevalent among older adults to manage chronic diseases and linked adverse geriatric outcomes, including physical cognitive functional impairments, falls, frailty, hospitalization, mortality. Deprescribing (withdrawal) a potential strategy polypharmacy. The broad molecular changes by which polypharmacy causes harm deprescribing may be beneficial are unknown unfeasible study rigorously in tissue from patients. Therefore, randomized controlled trial, we administered therapeutic doses commonly used medications (oxycodone, oxybutynin, citalopram, simvastatin, or metoprolol) as monotherapy concurrently (polypharmacy) middle-age (12 months) old-age (26 male C57BL/6J (B6) mice deprescribed (gradually withdrew) treatments subset age 21 months. We compared drug-related hepatic effects applying proteomics along with transcriptomics histology. found that on were limited but significant seen (93% unique polypharmacy). altered the expression proteins involved immunity, drug, cholesterol, amino acid metabolism, accompanied higher serum drug levels than monotherapies. not only reversed some also caused irreversible novel proteome. Furthermore, our identified several protein co-expressed modules associated clinically relevant such mobility, activities daily living. This highlights complex following aging, polypharmacy, deprescribing. Further exploration these mechanistic pathways inform management adults.

Language: Английский

Citations

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