Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections.
- 作者列表："Zhavoronkov A
:The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, géros "old man" and epilavís, "harmful") infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.
: 最近发现的导致SARS-CoV-2 大流行的新型冠状病毒肺炎倍他科病毒揭示了疾病负担中与年龄相关的脆弱性，并使老龄化研究成为焦点。现有的有限数据表明，新型冠状病毒肺炎应称为gerolavic (来自希腊语，g é ros “old man” 和epilavins，“有害”) 感染，因为感染率，严重程度，60 岁及以上人口的致死率明显更高。这主要是由于合并症，但可能部分是由于免疫衰老，老年人免疫功能下降，以及与衰老相关的功能、健康和虚弱增加的普遍丧失。免疫衰老是影响疫苗接种反应以及传染病的严重性和致死率的主要因素。虽然疫苗接种降低了感染率，并且治疗性干预降低了感染的严重性和致死率，但这些干预措施具有局限性。以前的研究表明，假定的geroprotectors，如西罗莫司 (雷帕霉素) 及其密切衍生物雷帕霉素依维莫司 (RAD001)，降低了老年患者的小样本感染率。本文综述了有关geroprotective和senormediative干预措施的有限文献，这些干预措施可用于降低gerolavic感染的疾病负担。本文还强调了需要严格的临床验证深度老化时钟作为生物年龄的替代标志物。这些可用于评估对geroprotective和senoremerative干预的需求和疗效，并为老年人群提供更好的保护，使其免受gerolavic感染。本文不代表医学建议，所描述的药物尚未获得许可或推荐作为免疫系统增强剂，因为它们尚未为此目的进行临床评估。
METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.