RESUMO
OBJECTIVE: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. METHODS: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. RESULTS: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. CONCLUSIONS: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.
Assuntos
Bombeiros , Humanos , Estados Unidos/epidemiologia , Envelhecimento/genética , Estudos Longitudinais , Leucócitos , Epigênese GenéticaRESUMO
We examine the use of the truncated singular value decomposition and Tikhonov regularization in standard form to address ill-posed least squares problems Ax = b that frequently arise in molecular mechanics force field parameter optimization. We illustrate these approaches by applying them to dihedral parameter optimization of genotoxic polycyclic aromatic hydrocarbon-DNA adducts that are of interest in the study of chemical carcinogenesis. Utilizing the discrete Picard condition and/or a well-defined gap in the singular value spectrum when A has a well-determined numerical rank, we are able to systematically determine truncation and in turn regularization parameters that are correspondingly used to produce truncated and regularized solutions to the ill-posed least squares problem at hand. These solutions in turn result in optimized force field dihedral terms that accurately parameterize the torsional energy landscape. As the solutions produced by this approach are unique, it has the advantage of avoiding the multiple iterations and guess and check work often required to optimize molecular mechanics force field parameters.