Downregulating Mitochondrial DNA Polymerase γ in the Muscle Stimulated Autophagy, Apoptosis, and Muscle Aging-Related Phenotypes in Drosophila Adults.

Reactive oxygen species, generated as by-products of mitochondrial electron transport, can induce damage to mitochondrial DNA (mtDNA) and proteins. Here, we investigated whether the moderate accumulation of mtDNA damage in adult muscles resulted in accelerated aging-related phenotypes in Drosophila. DNA polymerase γ (Polγ) is the sole mitochondrial DNA polymerase. The muscle-specific silencing of the genes encoding the polymerase subunits resulted in the partial accumulation of mtDNA with oxidative damage and a reduction in the mtDNA copy number. This subsequently resulted in the production of abnormal mitochondria with reduced membrane potential and, consequently, a partially reduced ATP quantity in the adult muscle. Immunostaining indicated a moderate increase in autophagy and mitophagy in adults with RNA interference of Polγ (PolγRNAi) muscle cells with abnormal mitochondria. In adult muscles showing continuous silencing of Polγ, malformation of both myofibrils and mitochondria was frequently observed. This was associated with the partially enhanced activation of pro-apoptotic caspases in the muscle. Adults with muscle-specific PolγRNAi exhibited a shortened lifespan, accelerated age-dependent impairment of locomotor activity, and disturbed circadian rhythms. Our findings in this Drosophila model contribute to understanding how the accumulation of mtDNA damage results in impaired mitochondrial activity and how this contributes to muscle aging.

An ultrasonographic estimated fetal weight reference for Japanese twin pregnancies.

PURPOSE: The purpose was to establish an estimated fetal weight (EFW) reference for twin pregnancies in Japan and to compare the growth of twins with singletons. METHODS: We retrospectively investigated Japanese women who delivered live-born twins at our center during the period from 2010 to 2016. The main exclusion criteria were monoamniotic twins, fetal reduction, maternal complications, twin-twin transfusion syndrome, fetal congenital anomalies, and patients with their first visit after 16 weeks' gestation. The EFW was measured longitudinally from 16 to 37 weeks' gestation. We calculated the posterior predictive distribution using hierarchical Bayesian models and determined the EFW corresponding to each Z-score. RESULTS: A total of 364 women (190 dichorionic and 174 monochorionic) were included, and the total number of examinations was 3952. The EFWs of a Z-score of 0 for twins at 20, 28, and 36 weeks' gestation were 308, 1070, and 2294 g, respectively. The EFW of a Z-score of 0 for twins was 98-101% that of singletons until 21 weeks, gradually becoming lower than that of singletons and reaching 90-93% that of singletons after 27 weeks. CONCLUSION: We established an EFW reference for Japanese twin pregnancies. The EFW of twins is similar to that of singletons until the mid-second trimester, gradually becoming lower than that of singletons and reaching about 90% that of singletons in the third trimester.