Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.

Telomere Length and Frailty: The Helsinki Birth Cohort Study.

OBJECTIVES: Telomere length is associated with aging-related pathologies. Although the association between telomere length and frailty has been studied previously, only a few studies assessing longitudinal changes in telomere length and frailty exist. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: A subpopulation of the Helsinki Birth Cohort Study consisting of 1078 older adults aged 67 to 79 years born in Helsinki, Finland, between 1934 and 1944. MEASURES: Relative leukocyte telomere length (LTL) was measured using quantitative real-time polymerase chain reaction at the average ages of 61 and 71 years, and at the latter the participants were assessed for frailty according to Fried criteria. RESULTS: The mean ± SD relative LTLs were 1.40 ± 0.29 (average age 61 years) and 0.86 ± 0.30 (average age 71 years) for the cohort. A trend of shorter mean relative LTL across frailty groups was observed at 61 years (P = .016) and at 71 years (P = .057). Relative LTL at age 61 years was significantly associated with frailty: per 1-unit increase in relative LTL, the corresponding relative risk ratio (RRR) of frailty was 0.28 (95% confidence interval [CI] 0.08-0.97), adjusting for several confounders. Also, LTL at age 71 years was associated with frailty (RRR 0.18, 95% CI 0.04-0.81) after adjustment for sex, age, and adult socioeconomic status, but further adjustment attenuated the association. No associations between telomere shortening and frailty were observed during the 10-year follow-up. CONCLUSIONS: Shorter relative LTL was associated with frailty in cross-sectional and longitudinal analyses, but telomere shortening was not, suggesting that short LTL may be a biomarker of frailty.

Fatty heart, cardiac damage, and inflammation.

Type 2 diabetes and obesity are associated with systemic inflammation, generalized enlargement of fat depots, and uncontrolled release of fatty acids (FA) into the circulation. These features support the occurrence of cardiac adiposity, which is characterized by an increase in intramyocardial triglyceride content and an enlargement of the volume of fat surrounding the heart and vessels. Both events may initially serve as protective mechanisms to portion energy, but their excessive expansion can lead to myocardial damage and heart disease. FA overload promotes FA oxidation and the accumulation of triglycerides and metabolic intermediates, which can impair calcium signaling, ß-oxidation, and glucose utilization. This leads to damaged mitochondrial function and increased production of reactive oxygen species, pro-apoptotic, and inflammatory molecules, and finally to myocardial inflammation and dysfunction. Triglyceride accumulation is associated with left ventricular hypertrophy and dysfunction. The enlargement of epicardial fat in patients with metabolic disorders, and coronary artery disease, is associated with the release of proinflammatory and proatherogenic cytokines to the subtending tissues. In this review, we examine the evidence supporting a causal relationship linking FA overload and cardiac dysfunction. Also, we disentangle the separate roles of FA oxidation and triglyceride accumulation in causing cardiac damage. Finally, we focus on the mechanisms of inflammation development in the fatty heart, before summarizing the available evidence in humans. Current literature confirms the dual (protective and detrimental) role of cardiac fat, and suggests prospective studies to establish the pathogenetic (when and how) and possible prognostic value of this potential biomarker in humans.

Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix.

Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.