Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as "damage-associated molecular pattern" (DAMP) agents and cause inflammation. As many elderly people are characterized by a low-grade, chronic inflammatory status defined "inflamm-aging," we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty-one Caucasian subjects were enrolled in the study, including 429 siblings aged 90-104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF-α, IL-6, RANTES, and IL-1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF-α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low-grade, chronic inflammation observed in elderly people.
Certain personality characteristics such as self-esteem, life satisfaction, and optimism are fundamental components of positive mental health status and well-being. There is consistent evidence that these traits tend to be substantially correlated in individuals. However, no previous studies have investigated the origin of such correlation. This research used the twin method to unravel the genetic and environmental architecture of self-esteem, life satisfaction, and optimism, along with their mutual interplay. The sample was derived from the population-based Italian Twin Register, and included 428 twin pairs, aged 23-24 years. Multivariate genetic modeling showed that genes influencing self-esteem, life satisfaction, and optimism are largely overlapping. Furthermore, results indicated that the environmental components of the traits may overlap only modestly, and suggested that a sizeable amount of variance in the traits may be explained by environmental effects specific to each of them.
Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) ¼ 12.2, 95% confidence interval (CI): 2.4 -62.3). A statistically significant association with additional birth defects, female gender and gestational age .40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR ¼ 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR ¼ 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease. 153 765-773
European Journal of Endocrinology
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