Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule

Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR). Importantly, this pathway was suppressed upon the induction of cellular senescence and in naturally aged cells, leading to a robust shutdown of mitophagy. Inhibition of mitophagy in proliferating cells was sufficient to trigger the senescence program, while reactivation of mitophagy was necessary for the anti-senescence effects of NAD precursors or rapamycin. Furthermore, reactivation of mitophagy by a p62-targeting small molecule rescued markers of cellular aging, which establishes mitochondrial quality control as a promising target for anti-aging interventions

Uso de medicamentos em crianças de zero a seis anos matriculadas em creches de Tubarão, Santa Catarina Drug utilization among children aged zero to six enrolled in day care centers of Tubarão, Santa Catarina, Brazil

OBJETIVO: Identificar o padrão de utilização de medicamentos, nos últimos seis meses, em crianças entre zero e seis anos, em quatro creches de Tubarão, Santa Catarina, no ano de 2007. MÉTODOS: Estudo transversal realizado por meio de questionário semi-estruturado, aplicado aos pais ou responsáveis pelas 413 crianças incluídas na pesquisa, após consentimento informado. Foram coletados dados sobre utilização de medicamentos e informações de saúde. A análise estatística foi feita com auxílio do programa Statistical Package for the Social Sciences 15.0. RESULTADOS: A média de idade das crianças foi 3,7±1,3 anos, sendo 195 (47%) meninas e 218 (53%) meninos. Dentre os adultos que responderam ao questionário, 75% eram mães e 43% tinham oito anos de estudo. Diante de situação de doença, 47% forneciam os medicamentos que tinham em casa. Das crianças pesquisadas, 82 (20%) apresentavam doença crônica e 75 (18%) portavam doença aguda no momento da pesquisa. Houve histórico de reações adversas aos medicamentos em 82 (20%) crianças, sendo a mais freqüente a alergia. A classe de medicamentos mais utilizada foi a dos analgésicos e antitérmicos (45%) e o motivo de uso principal foi febre (32%). Nos últimos seis meses, haviam sido utilizados 763 medicamentos, com média de 1,8 medicamentos por criança, sendo 41% com prescrição médica e 59% por automedicação. CONCLUSÕES: A prática freqüente de automedicação em crianças é um fenômeno potencialmente nocivo à saúde. Esse estudo mostrou que a maioria dos pais ou responsáveis segue essa prática, podendo mascarar doenças graves, gerar quadros de reações adversas e desenvolver resistência bacteriana, além de outras complicações.<br>OBJECTIVE: Identify the pattern of drug utilization in a six-month period among children aged zero to six years old, in Tubarão, Santa Catarina, Brazil, during 2007. METHODS: This cross-sectional study was carried out using a semi-structured questionnaire administered to parents or caretakers of 413 children included in the survey. After signing consent, parents were asked about the use of prescribed and over-the-counter medicines and other health information. Statistical Package for the Social Sciences 15.0 was used for statistical analysis. RESULTS: Out of 413 children, 195 (47%) were girls and 218 (53%) boys. Their mean age was 3.7±1.3 years. Most parents who answered the questionnaire were mothers (75%) and 43% had eight years of schooling. When asked about medication use in the event of diseases, 47% reported that they use medicines available at home. Among the children, 82 (20%) had chronic diseases and 75 (18%) presented an acute illness at the time of the study. Adverse drug reactions were reported by 82 (20%) of the caretakers, being allergy the most frequent. Antipyretics and analgesics were the medicines most frequently used (45%) in order to treat fever (32%). During the last six months, the use of 763 drugs was reported, corresponding to 1.8 drugs/child. Of these, 41% were prescribed by a physician and 59% as self medication. CONCLUSIONS: Parental frequent practice of self medication in treating children is potentially harmful to health. This study showed that most caretakers follow this practice which can mask serious diseases, provoke adverse reactions and develop bacterial resistance, among other complications