Globally 113 702 confirmed (4125 new) 4012 deaths (203 new) China 80 924 confirmed (20 new) 3140 deaths (17 new) Outside of China 32 778 confirmed (4105 new) 872 deaths (186 new) 109 countries/territories/ areas (5 new) WHO RISK ASSESSMENT China Very High Regional Level Very High Global Level Very High HIGHLIGHTS • 5 new countries/territories/areas (Brunei Darussalam, Mongolia, Cyprus, Guernsey and Panama) have reported cases of COVID-19 in the past 24 hours. 1 https://www.iatatravelcentre.com/international-travel-document-news/1580226297.htm 2 https://pandemic.internationalsos.com/2019-ncov/ncov-travel-restrictions-flight-operations-and-screening 3 https://www.iata.org/en/pressroom/pr/2020-03-02-01/ 4 https://www.who.int/ith/2019-nCoV_advice_for_international_traffic-rev/en/

The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.

BackgroundCurrent knowledge about elder mistreatment is mainly derived from studies done in Western countries, which indicate that this problem is related to risk factors such as a shared living situation, social isolation, disease burden, and caregiver strain. We know little about prevalence and risk factors for elder mistreatment and mistreatment subtypes in rural China where the elder population is the most vulnerable.MethodsIn 2010, we conducted a cross-sectional survey among older adults aged 60 or older in three rural communities in Macheng, a city in Hubei province, China. Of 2245 people initially identified, 2039 were available for interview and this was completed in 2000. A structured questionnaire was used to collect data regarding mistreatment and covariates. Logistic regression analysis was used to identify factors related to elder mistreatment and subtypes of mistreatment.ResultsElder mistreatment was reported by 36.2% (95% CI: 34.1%–38.3%) of the participants. Prevalence rates of psychological mistreatment, caregiver neglect, physical mistreatment, and financial mistreatment were 27.3% (95% CI: 25.3%–29.2%), 15.8% (95% CI: 14.2%–17.4%), 4.9% (95% CI: 3.9%–5.8%) and 2.0% (95% CI: 1.3%–2.6%), respectively. The multivariate logistic regression analysis revealed that depression, being widowed/divorced/single/separated, having a physical disability, having a labor intensive job, depending solely on self-made income, and living alone were risk factors for elder mistreatment. Different types of elder mistreatment were associated with different risk factors, and depression was the consistent risk factor for the three most common mistreatment subtypes.ConclusionOlder adults in rural China self-report a higher rate of mistreatment than their counterparts in Western countries. Depression is a main risk factor associated with most subtypes of mistreatment. Our findings suggest that prevention and management of elder mistreatment is a challenge facing a rapidly aging Chinese population.

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Cellular accumulation of DNA damage has been widely implicated in cellular senescence, aging, and premature aging. In Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD), premature aging is linked to accumulation of DNA double-strand breaks (DSBs) which results in genome instability. However, how DSBs accumulate in cells despite the presence of intact DNA repair proteins remains unknown. Here we report that the recruitment of DSB repair factors Rad50 and Rad51 to the DSB sites, as marked by γ-H2AX, was impaired in human HGPS and Zmpste24-deficient cells. Consistently, the progeria-associated DSBs appeared to be unrepairable although DSBs induced by camptothecin were efficiently removed in the progeroid cells. We also found that these progeroid cells exhibited nuclear foci of XPA, a unique nucleotide excision repair protein. Strikingly, these XPA foci colocalized with the DSB sites in the progeroid cells. This XPA-DSB association was further confirmed, and found to be mediated by DNA, using a modified chromatin immunoprecipitation assay and co-immunoprecipitation. RNAi knockdown of XPA in HGPS cells partially restored DSB repair as evidenced by Western blot analysis, immunofluorescence and comet assays. We propose that the uncharacteristic localization of XPA to or near DSBs inhibits DSB repair, thereby contributing to the premature aging phenotypes observed in progeria arising from genetic defects in prelamin A maturation.