The molecular impact of cigarette smoking resembles aging across tissues

• Type: Article in International Scientific Journal
• Date: 2025

Authors

Ramirez, JM (Author) Other; Ribeiro, R (Author) Other; Soldatkina, O (Author) Other; Moraes, A (Author) Other; García-Pérez, R (Author) Other; Ferreira, PG (Author) FCUP; Melé, M (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: GENOME MEDICINE

Vol. 17

ISSN: 1756-994X

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-011-6Q2

DOI: 10.1186/s13073-025-01485-x

Abstract (EN): BackgroundTobacco smoke is the main cause of preventable mortality worldwide. Smoking increases the risk of developing many diseases and has been proposed as an aging accelerator. Yet, the molecular mechanisms driving smoking-related health decline and aging acceleration in most tissues remain unexplored.MethodsHere, we use data from the Genotype-Tissue Expression Project (GTEx) to perform a characterization of the effect of cigarette smoking across human tissues. We perform a multi-tissue analysis across 46 human tissues. Our multi-omics characterization includes analysis of gene expression, alternative splicing, DNA methylation, and histological alterations. We further analyze ex-smoker samples to assess the reversibility of these molecular alterations upon smoking cessation.ResultsWe show that smoking impacts tissue architecture and triggers systemic inflammation. We find that in many tissues, the effects of smoking significantly overlap those of aging. Specifically, both age and smoking upregulate inflammatory genes and drive hypomethylation at enhancers (odds ratio (OR) = 2). In addition, we observe widespread smoking-driven hypermethylation at target regions of the Polycomb repressive complex (OR = 2), which is a well-known aging effect. Smoking-induced epigenetic changes overlap causal aging CpGs, suggesting that these methylation changes may directly mediate the aging acceleration observed in smokers. Finally, we find that smoking effects that are shared with aging are more persistent over time.ConclusionOverall, our multi-tissue and multi-omic analysis of the effects of cigarette smoking provides an extensive characterization of the impact of tobacco smoke across tissues and unravels the molecular mechanisms driving smoking-induced tissue homeostasis decline and aging acceleration.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23