RESUMO
BACKGROUND: Underage drinking and its effects have been researched extensively. However, no study to date has examined how the levels of drinking that have been defined as risky for adults might relate to youth who have a heightened physiological vulnerability to alcohol. OBJECTIVES: To examine a range of drinking measures that go beyond common measures of youth alcohol use to gain a more detailed understanding of the nature of underage drinking and its associated correlates and outcomes. METHODS: Analyzing data from a 2013 nationally representative US survey, we examined a variety of measures of alcohol use among 24,445 youth (weighted N = 381,155,562), the demographic groups most likely to have reported drinking in these ways, and associations between these measures of drinking and a number of adverse outcomes. RESULTS: On all measures of potentially risky drinking, including meeting diagnostic criteria for an alcohol use disorder, underage drinkers exceeded the rates found for adults. Independent of sex, race, and age, youth who reported drinking in ways that exceeded guidelines set for adults had increased odds of meeting diagnostic criteria for an alcohol, tobacco, or other drug use disorder, and of reporting a number of health problems. CONCLUSIONS: The high rates at which youth report engaging in a range of risky drinking behaviors suggest a need for a more nuanced approach to substance use and mental health screening and interventions in clinical practice. The findings also underscore the need to address apparent misconceptions about what constitutes unhealthy or unsafe alcohol use among youth.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Assunção de Riscos , Consumo de Álcool por Menores/estatística & dados numéricos , Adolescente , Comportamento do Adolescente/psicologia , Criança , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Crystallins are small heat shock proteins with chaperone function that prevent heat- and oxidative stress-induced aggregation of proteins. This is the first report describing modifications of alphaA crystallin in the sensory retina, including altered content and truncation with aging. Proteins from adult, middle age, and old Fischer 344 Brown Norway rats were compared. Western immunoblotting was used to evaluate alphaA crystallin content and identify protein spots on two-dimensional gels containing alphaA crystallin. The type and site of multiple post-translational modifications were identified by mass spectrometry. We found the content of alphaA crystallin was significantly decreased in the oldest rats. On two-dimensional gels, retinal crystallins resolved into multiple spots with altered migration, indicative of changes in intrinsic charge and/or truncation. Post-translational modifications that were identified included oxidation, phosphorylation, deamidation, acetylation, and truncation. In samples from rats of all ages, a highly modified N-terminus containing these modifications was found. We also observed an age-dependent difference in the extent of N- and C-terminal truncation. These results suggest that protection against stress-induced protein aggregation is compromised in the aged retina.
Assuntos
Envelhecimento/metabolismo , Retina/química , Retina/metabolismo , Deleção de Sequência/fisiologia , Cadeia A de alfa-Cristalina/química , Cadeia A de alfa-Cristalina/metabolismo , Envelhecimento/genética , Sequência de Aminoácidos , Animais , Western Blotting , Regulação para Baixo/fisiologia , Masculino , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Ratos , Ratos Endogâmicos F344 , Cadeia A de alfa-Cristalina/biossíntese , Cadeia A de alfa-Cristalina/genéticaRESUMO
Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type 1 fibers in soleus muscle. Determination of proteasome function showed hydrolysis of fluorogenic peptides was equivalent between ages. However, when accounting for the 3-fold increase in content of the 20S catalytic core in aged muscle, the lower specific activity suggests a functional loss in individual proteins with aging. Comparing the composition of the catalytic beta-subunits showed an age-related 4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of the activating complexes, PA28 and PA700, relative to the 20S proteasome was reduced 50%. These results suggest significant alterations in the intrinsic activity, the percentage of immunoproteasome, and the regulation of the 20S proteasome by PA28 and PA700 in aged muscle.