Molecular pathology of aging and its implications for senescent coronary atherosclerosis.
ABSTRACT This review highlights common mechanisms of organismal aging and inflammatory coronary atherosclerosis.
A substantial body of evidence now indicates that aging is largely due to molecular damage inflicted by reactive oxygen species, electrophiles, and other reactive endobiotic and xenobiotic metabolites. Our understanding of genetic pathways regulating longevity began 12 years ago with the discovery that a developmental-arrest program in the nematode Caenorhabditis elegans also has marked effects on adult lifespan. This pathway, closely related to the insulin and insulinlike growth factor-signaling pathways of mammals, modulates longevity and stress resistance in several model organisms. Insulin-like signaling also has an impact on redox signaling, antioxidant defenses, and metabolic generation of oxidative stress. Recently, additional signaling pathways--involving Sirtuins, AMP kinase, Jun N-terminal kinase 1, and other master regulatory proteins--have been implicated in longevity and stress-resistance mechanisms. The inflammatory process involves acute production of reactive oxygen species by specialized cells responding to infection, exposure to toxins or allergens, cell damage, hypoxia, ischemia/reperfusion, and other factors, initiating signaling through several of these pathways. Free radical chain reactions arise from lipid oxidation and generate oxidized low-density lipoprotein, a powerful inflammatory signal and potentiator of atherosclerosis. Oxidized low-density lipoprotein accumulates in atherosclerotic arteries, particularly in rupture-prone regions. Inflammation involving oxidative stress, by way of the production of reactive oxygen species, is a hallmark of coronary atherosclerosis.
Common pathways underlie both organismal aging and tissue-autonomous senescent pathologic processes, such as coronary atherosclerosis. The mechanisms discovered in model organisms may lead to pharmacotherapeutic interventions.
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ABSTRACT: Background and objective Recently, the prevalence of colorectal neoplasm is increasing sharply. It has been reported that both colorectal neoplasm and cardiovascular disease share similar common risk factors. Subclinical hypothyroidism (SCH) occurs in 4–20% of the adult population and is an independent risk factor for cardiovascular disease. However, no study has yet explored the relationship between SCH and colorectal neoplasm. Our objectives were to clarify the association between the two conditions. Methods This is a case-control study. A total of 273 cases of colorectal neoplasm were first identified, and a 1:3 matched random sample of 819 controls was then collected using strata according to age, and gender. The medical records of all these patients were retrieved. Blood pressure, body mass index, and thyroid function were determined. Colonoscopies were performed by experienced gastroenterologists. A logistic regression analysis was carried out to explore the relationship between SCH and colorectal neoplasm. Results Remarkably, the prevalence rate of SCH was significantly higher in colorectal neoplasm (+) group, compared with colorectal neoplasm (−) group (P < 0.01). Colorectal neoplasm was found in 67 (34.9%) subjects in SCH group, which was more than that in euthyroid group (P = 0.002). Moreover, patients with SCH were more likely to have advanced colonic lesion and colorectal cancer compared with euthyroid subjects (P = 0.028 and 0.036, respectively). After adjusting for the factors of blood pressure, body mass index, history of hypertension and smoking, an association still existed between colorectal neoplasm and SCH (OR = 1.689, 95% CI: 1.207–2.362, P = 0.002). Conclusion A strong association between SCH and colorectal neoplasm was firstly identified. SCH was found to be an independent risk factor for colorectal neoplasm.Gastroentérologie Clinique et Biologique 09/2014; DOI:10.1016/j.clinre.2014.08.002 · 1.98 Impact Factor
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ABSTRACT: Recent evidence from apolipoprotein E-deficient (apoE-/-) mice shows that aging and atherosclerosis are closely associated with increased oxidative stress and DNA damage in some cells and tissues. However, bone marrow cells, which are physiologically involved in tissue repair have not yet been investigated. In the present study, we evaluated the influence of aging and hypercholesterolemia on oxidative stress, DNA damage and apoptosis in bone marrow cells from young and aged apoE-/- mice compared with age-matched wild-type C57BL/6 (C57) mice, using the comet assay and flow cytometry. The production of both superoxide and hydrogen peroxide in bone marrow cells was higher in young apoE-/- mice than in age-matched C57 mice, and reactive oxygen species were increased in aged C57 and apoE-/- mice. Similar results were observed when we analyzed the DNA damage and apoptosis. Our data showed that both aging and hypercholesterolemia induce the increased production of oxidative stress and consequently DNA damage and apoptosis in bone marrow cells. This study is the first to demonstrate a functionality decrease of the bone marrow, which is a fundamental extra-arterial source of the cells involved in vascular injury repair.International Journal of Molecular Sciences 02/2013; 14(2):3325-42. DOI:10.3390/ijms14023325 · 2.34 Impact Factor
Archives des Maladies du Coeur et des Vaisseaux - Pratique 05/2009; 2009(177):22-23. DOI:10.1016/S1261-694X(09)73974-4