[Everyday competencies and learning processes in old age. Results and perspectives of the PIAAC extension study "Competencies in later life"]. / Alltagskompetenzen und Lernprozesse im höheren Lebensalter. Ergebnisse und Perspektiven der PIAAC-Erweiterungsstudie "Competencies in Later Life".

This article deals with the study "Competencies in later life" (CiLL), a parallel study to the German program for the international assessment of adult competencies (PIAAC) survey which assesses the level and distribution of skills of the adult population in a representative study. Assuming the growing importance of learning and education in a society challenged by demographic changes, the first section of the paper outlines the qualitative research of learning activities of focus groups in the daily life of elderly people. The second section of the paper presents the survey design and exemplary findings of the quantitative CiLL study. Initial results show that basic skills of the elderly are highly influenced by personal and sociodemographic variables, particularly by educational background. The data available indicate that the participation of the elderly in adult education and the options available for competence development have to be increased.

Gene expression and immunohistochemistry in adipose tissue of HIV type 1-infected patients with nucleoside analogue reverse-transcriptase inhibitor-associated lipoatrophy.

BACKGROUND: Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms. METHODS: Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed. RESULTS: mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group. CONCLUSIONS: Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices.

OBJECTIVES: Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy. METHODS: Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial. RESULTS: Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry. CONCLUSION: In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.

Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats.

BACKGROUND AND PURPOSE: Doxorubicin causes a chronic cardiomyopathy in which reactive oxygen species (ROS) accumulate over time and are associated with genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective iron chelator that interferes with ROS production. We aim to analyze the effects of dexrazoxane on mitochondria in the prevention of doxorubicin-induced chronic myocardial lesions. EXPERIMENTAL APPROACH: Wistar rats (11 weeks of age) were injected with intravenous doxorubicin (0.8 mg kg(-1) weekly for 7 weeks) with or without simultaneous dexrazoxane (8 mg kg(-1)). Animals were killed at 48 weeks. Cardiomyopathy was scored clinically and histologically and cardiac mitochondria were analyzed. KEY RESULTS: Compared to control rats receiving saline, rats treated with doxorubicin alone developed a clinical, macroscopic, histological and ultrastructural cardiomyopathy with low cytochrome c-oxidase (COX) activity (26% of controls). The expression of the mtDNA-encoded COX II subunit was reduced (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde 338% and superoxide 787% of controls). Mitochondria were depleted of mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated levels of mtDNA deletions. Dexrazoxane co-administration prevented all these effects of doxorubicin on mitochondria, except that hearts co-exposed to doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls) and mtDNA deletions at low frequency. CONCLUSIONS AND IMPLICATIONS: Dexrazoxane prevented doxorubicin induced late-onset cardiomyopathy and also protected the cardiac mitochondria from acquired ultrastructural, genetic and functional damage.

Mitochondrial DNA depletion in liver tissue of patients infected with hepatitis C virus: contributing effect of HIV infection?

OBJECTIVES: It has been suggested that chronic hepatitis C virus (HCV) infection depletes mitochondrial DNA (mtDNA) in the liver. Because decreased mtDNA levels were also found in humans infected with HIV, we investigated whether HIV may have aggravated hepatic mtDNA depletion in individuals with HCV infection. METHODS: In this cross-sectional study, liver biopsies were performed in a total of 40 individuals prior to any antiviral therapy. The individuals were recruited from the Hospital Clinic, Barcelona and the HIV Centre, Dusseldorf. Seventeen patients were negative for HIV and HCV and were biopsied for liver enzyme elevation of unknown cause (controls), 14 individuals had chronic HCV but no HIV infection, and nine subjects were coinfected with both viruses. mtDNA and liver histology were centrally assessed. RESULTS: The groups did not differ with respect to age, gender, liver function tests and HCV viral load, where applicable. mtDNA levels were decreased by 19% in the HCV-monoinfected group (P=0.03) and by 27% in the HIV/HCV-coinfected subjects (P=0.02) compared to controls. The mtDNA content, however, did not differ between individuals with HCV monoinfection and HCV/HIV coinfection (P=0.75). The degrees of liver fibrosis, inflammatory activity or steatosis did not correlate with mtDNA content. CONCLUSIONS: Liver mtDNA content is reduced in both HCV-monoinfected and HIV/HCV-coinfected patients. Under the limitations of our study, we could demonstrate only a slight trend towards more pronounced mtDNA depletion in HIV/HCV-coinfected subjects.

Effects of of didanosine-related depletion of mtDNA in human T lymphocytes.

The normal metabolism of mitochondria in T lymphocytes is unknown, as are the effects from nucleoside-analogue reverse-transcriptase inhibitors that impair mitochondrial polymerase- gamma . We isolated peripheral-blood CD4 and CD8 T lymphocytes from 6 healthy men and stimulated them with anti-CD3 and anti-CD28 antibodies, in the presence and in the absence of didanosine (ddI). In the absence of ddI, mitosis of T lymphocytes was paralleled by a transient up-regulation of both mtDNA and production of lactate. In CD4 lymphocytes, 10-day incubation with ddI at concentrations of 11.8 mu mol/L, 35.4 mu mol/L, 59.0 mu mol/L, and 118.0 mu mol/L induced (1) a concentration-dependent reduction of both mtDNA (to 73%, 29%, 24%, and 23%, respectively, of the levels in control samples) and subunit II of mtDNA-encoded cytochrome c oxidase (to 86%, 81%, 55%, and 31%, respectively, of the levels in control samples) and (2) a concentration-dependent increase in production of lactate (to 139%, 222%, 276%, and 312%, respectively, of the levels in control samples). Activation of lymphocytes (which was measured in terms of expression of CD25) was unaffected. Mitochondrial depolarization (assessed by staining with JC-1) was observed as early as day 7 of incubation. All changes were time dependent and also were observed in isolated CD8 lymphocytes. Electron microscopy revealed enlarged mitochondria with vacuoles, inclusions, and reduced electron density. ddI at a concentration of 11.8 mu mol/L induced changes that bordered statistical significance. After stimulation, there was a wide range in the change of mtDNA content in lymphocytes. Therefore, mtDNA measurements in blood are not necessarily a marker for the mitochondrial toxicity of ddI. Nevertheless, ddI does lead to depletion of mtDNA in lymphocytes and to functional impairment.