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Positive models of aging, including aging well, and active, healthy or successful aging models, are increasingly receiving attention from gerontologists and geriatricians. Yet important challenges remain in defining and measuring positive aging consistently and in line with older adults’ perspectives for research, practice and policy purposes. The primary objective of this study was to develop a person-centered index of aging well that integrates previous research on lay perspectives, and to examine the social determinants of this index in an effort to promote health and social policies that maximize the well being of older adults. We conducted secondary analyses of large national databases collected in 2014 across North America, namely the U.S. Health and Retirement Study (N= 3,463), the Canadian Longitudinal Study on Aging (N=18,553), and the Mexican Healthy Aging Study (N=6,456). Starting from qualitative evidence in all three countries, we constructed a composite index capturing lay perspectives. The index proposed is a continuous score, and contains health-related components such as disability in activities of daily living and mobility, pain, self-rated health, and cognitive function, as well as psychosocial components such as mood, productive activities, social relations, and life satisfaction. Mean scores on the index were 69.9(SD 14.2) in the US, 56.34 (17.03 SD) in Mexico, and 79.8 (SD 10.7) in Canada. Men had significantly higher scores in all countries. While there were notable differences in effect sizes, income, education, tobacco use, and physical exercise were important determinants of aging well across North American countries.

Myotonic dystrophy (DM1) is caused by the expansion of a trinucleotide repeat (CTG) located in the 3 0 untranslated region of the myotonic dystrophy protein kinase gene, for which currently there is no effective treatment. The data available suggest that misregulation of RNA homeostasis may play a major role in DM1 muscle pathogenesis. This indicates that the specific targeting of the mutant DMPK transcripts is essential to raise the rationale basis for the development of a specific gene therapy for DM1. We have produced a retrovirus which expresses a 149-bp antisense RNA complementary to the (CUG)13 repeats and to the 110bp region following the repeats sequence to increase the specificity. This construct was introduced into human DM1 myoblasts, resulting in a preferential decrease in mutant DMPK transcripts, and effective restoration of human DM1 myoblast functions such as myoblast fusion and the uptake of glucose. It was previously shown that delay of muscle differentiation and insulin resistance in DM1 are associated with misregulation of CUGBP1 protein levels. The analysis of CUGBP1 levels and activity in DM1 cells expressing the antisense RNA indicated a correction of CUGBP1 expression in infected DM1 cells. We therefore show that current antisense RNA delivered in vitro using a retrovirus is not only capable of inhibiting mutant DMPK transcripts, but also can ameliorate dystrophic muscle pathology at the cellular levels.

One of the earliest events in the process of leaf senescence is dismantling of chloroplasts. Mesophyll cell chloroplasts from rosette leaves were studied in Arabidopsis thaliana undergoing natural senescence. The number of chloroplasts decreased by only 17% in fully yellow leaves, and chloroplasts were found to undergo progressive photosynthetic and ultrastructural changes as senescence proceeded. In ultrastructural studies, an intact tonoplast could not be visualized, thus, a 35S-GFP::delta-TIP line with a GFP-labeled tonoplast was used to demonstrate that chloroplasts remain outside of the tonoplast even at late stages of senescence. Chloroplast DNA was measured by real-time PCR at four different chloroplast loci, and a fourfold decrease in chloroplast DNA per chloroplast was noted in yellow senescent leaves when compared to green leaves from plants of the same age. Although chloroplast DNA did decrease, the chloroplast/nuclear gene copy ratio was still 31:1 in yellow leaves. Interestingly, mRNA levels for the four loci differed: psbA and ndhB mRNAs remained abundant late into senescence, while rpoC1 and rbcL mRNAs decreased in parallel to chloroplast DNA. Together, these data demonstrate that, during senescence, chloroplasts remain outside of the vacuole as distinct organelles while the thylakoid membranes are dismantled internally. As thylakoids were dismantled, Rubisco large subunit, Lhcb1, and chloroplast DNA levels declined, but variable levels of mRNA persisted.