Mitochondria and aging in older individuals: an analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study.

Population aging is a looming global health challenge. New biological aging metrics based on DNA methylation levels have been developed in addition to traditional aging biomarkers. The prospective relationships of aging biomarkers with mitochondrial changes are still not well understood. Here, we examined the prospective associations of mitochondrial copy number (mtDNAcn) with several aging biomarkers - DNAm-Age, DNAm-PhenoAge, DNAm-GrimAge, and leukocyte telomere length. We analyzed 812 individuals from Veteran Affairs Normative Aging Study (NAS) with available blood samples from 1999-2013. Whole blood mtDNAcn and relative leukocyte telomere length were measured via qPCR. DNA methylation was assessed and used to calculate DNAm-Age, DNAm-GrimAge, and DNAm-PhenoAge. Linear mixed models were used to quantify the associations of mtDNAcn with DNAm-Age, DNAm-GrimAge, DNAm-PhenoAge, and leukocyte telomere length. In multivariable cross-sectional analyses, mtDNAcn is negatively associated with DNAm-Age PhenoAge and DNAm-PhenoAge. In contrast, mtDNAcn is associated with prospective measures of higher DNAm-PhenoAge and shorter leukocyte telomere length. Our study shows that higher mtDNAcn is associated with prospective measures of greater DNAm-PhenoAge and shorter leukocyte telomere length independent of chronological age. This indicates a role for mitochondrial in aging-related disease and mortality, but not the departure of biological age from chronological age.

Bayesian model averaging in time-series studies of air pollution and mortality.

The issue of model selection in time-series studies assessing the acute health effects from short-term exposure to ambient air pollutants has received increased scrutiny in the past 5 yr. Recently, Bayesian model averaging (BMA) has been applied to allow for uncertainty about model form in assessing the association between mortality and ambient air pollution. While BMA has the potential to allow for such uncertainties in risk estimates, Bayesian approaches in general and BMA in particular are not panaceas for model selection., Since misapplication of Bayesian methods can lead to erroneous conclusions, model selection should be informed by substantive knowledge about the environmental health processes influencing the outcome. This paper examines recent attempts to use BMA in air pollution studies to illustrate the potential benefits and limitations of the method.

Identification of quantitative trait loci for chemical/inflammatory nociception in mice.

Sensitivity to pain is widely variable, and much of this variability is genetic in origin. The specific genes responsible have begun to be identified, but only for thermal nociception. In order to facilitate the identification of polymorphic, pain-related genes with more clinical relevance, we performed quantitative trait locus (QTL) mapping studies of the most common assay of inflammatory nociception, the formalin test. QTL mapping is a technique that exploits naturally occurring variability among inbred strains for the identification of genomic locations containing genes contributing to that variability. An F2 intercross was constructed using inbred A/J and C57BL/6J mice as progenitors, strains previously shown to display resistance and sensitivity, respectively, to formalin-induced nociception. Following phenotypic testing (5% formalin, 25 microl intraplantar injection), mice were genotyped at 90 microsatellite markers spanning the genome. We provide evidence for two statistically significant formalin test QTLs - chromosomal regions whose inheritance is associated with trait variability - on distal mouse chromosomes 9 and 10. Identification of the genes underlying these QTLs may illuminate the basis of individual differences in inflammatory pain, and lead to novel analgesic treatment strategies.

Talidomida no tratamento das neovascularizaçöes sub-foveolares: relato de casos / Thalidomide in the treatment of subfoveal neovascularization: case reports

O objetivo deste trabalho foi o de relatar 4 pacientes que utilizam, durante 6 meses, 100mg/dia de Talidomida para o tratamento de neovascularizaçäo sub-foveolar, relacionada à idade, e, também, idiopática ou inflamatória. Todos foram seguidos regularmente por um clínico e autorizaram o teste terapêutico. Näo houve para-efeito que justificasse a interrupçäo da droga. Em dois olhos houve progressäo do crescimento neovascular. Os outros casos näo exibiram regressäo do quadro, apenas reduçäo discreta das anormalidades clinico-angiográficas