警告 コロナワクチンによるコロナ感染予防の対価は急激な老化促進

僕の知り合いも接種後見るからに老化した。

RT アメリカで去年末に接種した50代の医師の友人が、子どもでも分かる程の速さで老けて、髪の毛もチリチリになって、最近は足が悪くなり杖をつき始めました。こんな事になるのでしょうか？

— 苫米地英人 (@DrTomabechi) September 11, 2021

 

SARS-CoV-2 vaccines: Lights and shadows

Abstract

Vaccines to prevent acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicit an immune neutralizing response. Some concerns have been raised regarding the safety of SARS-CoV-2 vaccines, largely based on case-reports of serious thromboembolic events after vaccination. Some mechanisms have been suggested which might explain the adverse cardiovascular reactions to SARS-CoV-2 vaccines. Different vaccine platforms are currently available which include live attenuated vaccines, inactivated vaccines, recombinant protein vaccines, vector vaccines, DNA vaccines and RNA vaccines. Vaccines increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized, the Spike proteins assembled in the cytoplasma migrate to the cell surface and protrude with a native-like conformation. These proteins are recognized by the immune system which rapidly develops an immune response. Such response appears to be quite vigorous in the presence of DNA vaccines which encode viral vectors, as well as in subjects who are immunized because of previous exposure to SARS-CoV-2. The resulting pathological features may resemble those of active coronavirus disease. The free-floating Spike proteins synthetized by cells targeted by vaccine and destroyed by the immune response circulate in the blood and systematically interact with angiotensin converting enzyme 2 (ACE2) receptors expressed by a variety of cells including platelets, thereby promoting ACE2 internalization and degradation. These reactions may ultimately lead to platelet aggregation, thrombosis and inflammation mediated by several mechanisms including platelet ACE2 receptors. Whereas Phase III vaccine trials generally excluded participants with previous immunization, vaccination of huge populations in the real life will inevitably include individuals with preexisting immunity. This might lead to excessively enhanced inflammatory and thrombotic reactions in occasional subjects. Further research is urgently needed in this area.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084611/

April 3, 2020

The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular DiseaseInsights From Cardiovascular Aging Science

Majd AlGhatrif, MD, MA^1,2; Oscar Cingolani, MD³; Edward G. Lakatta, MD¹

Author Affiliations Article Information

JAMA Cardiol. 2020;5(7):747-748. doi:10.1001/jamacardio.2020.1329

As we brace for the imminent impact of the coronavirus disease 2019 (COVID-19) pandemic, we are faced with a controversy on how to best minimize the risk of lethal disease among the most vulnerable of us. Preliminary epidemiological data show an uneven-handed impact on the population, with an exponential increase in disease severity and mortality in those beyond the sixth decade of life with cardiovascular disease (CVD) and diabetes. Given that angiotensin-converting enzyme 2 (ACE2), an enzyme coopted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter epithelial cells, is upregulated in patients with CVD and diabetes treated with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), it was proposed that this increase in ACE2 expression underpins the greater COVID-19 severity in this population. This has created substantial controversy regarding the approach to patients taking ACEIs/ARBs in preparation for the pandemic, with some advocating for discontinuing these medications while expert opinions recommended against discontinuation, given the lack of strong evidence.¹

To begin to unravel this complex dilemma, we must consider the role of ACE2 not only in COVID-19 pathogenesis but also as a component of renin-angiotensin system (RAS) signaling throughout the body. First, one must recognize the scarcity of data on the topic, particularly in humans. Nonetheless, the urgency of the situation makes it imperative to use inductive reasoning to guide our next steps toward protecting our patients. It is well established now that while ACE2 is targeted by SARS-CoV-2 to gain entrance into cells, it plays a major anti-inflammatory role in RAS signaling by converting angiotensin II, the quintessential perpetrator of inflammation,² to angiotensin 1-7, which carries anti-inflammatory properties.³

What has been missing in discussions of the aforementioned dilemma is the age-associated decline in ACE2 expression, as observed in the lungs of rats,⁴ which is in line with a constellation of major proinflammatory changes perpetrated by an age-associated increase in RAS signaling throughout the body.⁵ Exaggerated forms of this proinflammatory profile are also salient pathophysiologic features of hypertension and diabetes, which are highly prevalent at older ages.⁵ The upregulation of ACE2 in individuals with diabetes and hypertension treated with ACEIs/ARBs is, in a way, restorative of physiological function. Hence, these observations raise an apparent paradox: given ACE2 itself is the gateway of SARS-CoV-2 entry into cells, how can the reduction in ACE2 levels in older persons and those with CVD predispose for greater COVID-19 severity?

This apparent paradox becomes clear if we distinguish the role of ACE2 as a gateway for SARS-CoV-2 facilitating the infection from its pivotal anti-inflammatory function in RAS signaling that is compromised in individuals with COVID-19, contributing to its severity (Figure).³ Indeed, data on the severe acute respiratory syndrome epidemic of 2003 demonstrates this divergence in factors predisposing to disease occurrence and its severity; in the former epidemic, although younger individuals in their third and fourth decades of life accounted for most of those infected,⁶ these younger patients had lower disease severity and risk of mortality compared with older people with preexisting conditions.

 

　

https://jamanetwork.com/journals/jamacardiology/fullarticle/2764300

 

Ageing, ACE2 deficiency and bad outcome in COVID-19

Fabio Angeli , Gianpaolo Reboldi and Paolo Verdecchia

From the journal Clinical Chemistry and Laboratory Medicine (CCLM)

https://doi.org/10.1515/cclm-2021-0658

Some phenotypes associated with severe forms of COVID-19 share a variable degree of ACE2 deficiency [6]. It has been suggested that the loss of ACE2 enzymatic activity (mediated by the interaction between ACE2 and SARS-CoV-2 Spike proteins) is particularly detrimental among patients with baseline ACE2 deficiency for the consequent marked imbalance between angiotensin II and angiotensin_1,7 [6]. Specifically, phenotypes of lower ACE2 expression are identified by the presence of hypertension, diabetes, cardiovascular disease and, notably, older age [6].

Ageing has been associated with decline in levels of ACE2 expression in experimental and human models [8], [9], [10]. Ageing-related decrease in ACE2 expression levels was observed in lung epithelial cells of aged rats compared to young rats [9]. Xie and co-workers [9] determined the characteristic of ACE2 expression in lung and the effect of ageing on its expression among rats at three distinct ages (young-adult, 3 months; middle-aged, 12 months; old, 24 months). ACE2 was predominantly expressed in alveolar epithelium, bronchiolar epithelium, endothelium and smooth muscle cells of pulmonary vessels with similar content [9]. The decrease of ACE2 content was relatively slight between young-adult and middle-aged groups [9]. Conversely, ACE2 expression was markedly reduced among older group (young-adult vs. old: by 78% in male rats and 67% in female rats, p<0.001; middle-aged vs. old: by 71% in male rats and 59% in female rats, p<0.001) [9].

Similarly, a study by Yoon and coworkers [8] evaluated the association between the change in the expression of ACE2 and arterial ageing in mice. Levels of ACE2 were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results demonstrated that the expressions of ACE2 decreased with age [8].

A bioinformatic analysis of publicly available human genomics and transcriptomics gene expression data by Chen and coworkers [10] demonstrated that ACE2 expression decreases during ageing in many tissues. Specifically, the Authors documented a decrease in ACE2 expression with age in blood, adrenal gland, colon, nervous system, adipose tissues, and salivary gland [10]. They also documented a significant association of age, sex, ethnic groups, and body mass index (BMI) with ACE2 expression. However, the association with age was the strongest followed by sex, ethnicity, and BMI [10].

https://www.degruyter.com/document/doi/10.1515/cclm-2021-0658/html

コロナ感染かワクチンで老化促進して他の原因で死ぬか・・・

まあそういふチョイスです。（爆ｗｗｗｗｗｗｗｗｗｗｗｗ