RESUMEN
The purpose of this study was to determine differences in somatosensation between older adults with and without type 2 diabetes among three age groups (60s, 70s, and 80s). We recruited 67 adults with type 2 diabetes and 67 age-matched adults without diabetes, aged 60-85. Data were collected using measures in Somatosensory Domain of the National Institute of Health (NIH) Toolbox. We found significant differences in the total scores of five tests examining kinesthesia, tactile sensation, and stereognosis among the three age groups. For all significant differences, the nondiabetes group and those in their 60s and 70s had better functioning than the diabetes group and those in their 80s. The NIH Toolbox-Somatosensory Tools used in this study may be more suitable to discriminate among age groups rather than diagnostic groups.
Asunto(s)
Envejecimiento/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/etiología , Trastornos Somatosensoriales/diagnóstico , Trastornos Somatosensoriales/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Australia , Femenino , Humanos , Kansas , Masculino , Persona de Mediana Edad , Ohio , PennsylvaniaRESUMEN
It is important that chromosomes are duplicated only once per cell cycle. Over-replication is prevented by multiple mechanisms that block the reformation of a pre-replicative complex (pre-RC) onto origins in S and G2 phase. We have investigated the developmental regulation of Double-parked (Dup) protein, the Drosophila ortholog of Cdt1, a conserved and essential pre-RC component found in human and other organisms. We find that phosphorylation and degradation of Dup protein at G1/S requires cyclin E/CDK2. The N terminus of Dup, which contains ten potential CDK phosphorylation sites, is necessary and sufficient for Dup degradation during S phase of mitotic cycles and endocycles. Mutation of these ten phosphorylation sites, however, only partially stabilizes the protein, suggesting that multiple mechanisms ensure Dup degradation. This regulation is important because increased Dup protein is sufficient to induce profound rereplication and death of developing cells. Mis-expression has different effects on genomic replication than on developmental amplification from chorion origins. The C terminus alone has no effect on genomic replication, but it is better than full-length protein at stimulating amplification. Mutation of the Dup CDK sites increases genomic re-replication, but is dominant negative for amplification. These two results suggest that phosphorylation regulates Dup activity differently during these developmentally specific types of DNA replication. Moreover, the ability of the CDK site mutant to rapidly inhibit BrdU incorporation suggests that Dup is required for fork elongation during amplification. In the context of findings from human and other cells, our results indicate that stringent regulation of Dup protein is critical to protect genome integrity.