First, a friendly warning; some information below is probably for many very surprising and perhaps even worrying! See * a few lines further down
NB! If you, who read above, feel insecure, please email me at info@stressmedicin.se – below is not easy to understand, given you do not have in-depth science-knowledge and clinically based training!
* But sometimes new knowledge challenges what we may have taken for granted, which turns out to be perhaps destructive. This applies to critically reviewing even when it comes to completely new perspectives, see e.g. Paradigm | Biopsychosocial Medicine or the problems surrounding Confirmation Bias (www.culturalmedicine.se, basically = you only believe what you already believe – within your private/scientific/clinical paradigm, – which you think is right wihout often not even realize it), A huge problem for health care? Confirmation bias, placebo/nocebo vs reductionistic medicine | Biopsychosocial Medicine – A major problem in virtually all education is that many people perceive the knowledge (and related practice) that is taught is precise knowledge, which it is not without different degrees of “safe knowledge”. Even worse is if the teacher believes that this(e) teaches absolute knowledge without varying degrees of deficient that the teacher himself more or less understood. NOTE it is not black or white, if you walk across a street with traffic all the time you should not go straight out without looking! The same applies to all types of learning – it is important to look for and critically review before accepting the “paradigm” taught – see above link! NB! If you who read above feel insecure, feel free to email me at info@stressmedicin.se – above is not easy to understand, given you do not have in-depth scientifically-based training!
My own notes; Inflammaging is a word “founded” year 2000, but we have suspect that not only inflammation is critical in general for a sound health development but also that it may be developing over the years in way complicating even more its consequences on development and sustaining health as well as many kinds of dysfunctions.
As now increasing knowledge integrate mitochondria and inflammation where also quantum biology (The quantum mitochondrion and optimal health – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264502/) begin to play an important role in understanding aging and health, we can see the below as the beginning of the beginning in a revolution which so far is quite silent. As always, we should be careful with existing knowledge (which is not complex/absolute) as well as with new knowledge. E:g. www.mitoQ.com (NB it is not only for sports but very much also for aging) is a an interesting development to influence mitochondria function, which I myself has tested for a few years carefully and will probably recommend use of MitoQ soon – perhaps I am to careful, but I do think it “pay-off” over time. Often we can get enthusiastic and move too fast and sometimes too carful .. important to find a way in between.
Inflamm-aging. An evolutionary perspective on immunosenescence
(2000) “In this paper we extend the ”network theory of aging,” and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as ”inflamm-aging,” is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response”. https://pubmed.ncbi.nlm.nih.gov/10911963/
(2020) – Age-related cerebral small vessel disease and Inflammaging – https://www.nature.com/articles/s41419-020-03137-x?elqTrackId=c172648eefc748deae1322fee525e44c see PDF
“The continued increase in global life expectancy predicts a rising prevalence of age-related cerebral small vessel diseases (CSVD), which requires a better understanding of the underlying molecular mechanisms. In recent years, the concept of “inflammaging” has attracted increasing attention. It refers to the chronic sterile low-grade inflammation in elderly organisms and is involved in the development of a variety of age-related chronic diseases. Inflammaging is a long-term result of chronic physiological stimulation of the immune system, and various cellular and molecular mechanisms (e.g., cellular senescence, immunosenescence, mitochondrial dysfunction, defective autophagy, metaflammation, gut microbiota dysbiosis) are involved. With the deepening understanding of the etiological basis of age-related CSVD, inflammaging is considered to play an important role in its occurrence and development. One of the most critical pathophysiological mechanisms of CSVD is endothelium dysfunction and subsequent blood-brain barrier (BBB) leakage, which gives a clue in the identification of the disease by detecting circulating biological markers of BBB disruption. The regional analysis showed blood markers of vascular inflammation are often associated with deep perforating arteriopathy (DPA), while blood markers of systemic inflammation appear to be associated with cerebral amyloid angiopathy (CAA). Here, we discuss recent findings in the pathophysiology of inflammaging and their effects on the development of age-related CSVD. Furthermore, we speculate the inflammaging as a potential target for future therapeutic interventions to delay or prevent the progression of the age-related CSVD.”
NB above can be understood somewhat different depending on what paradigm is used as platform. I clarify how we define the paradigm of Biopsychosocial Stress Medicine at Definition | Biopsychosocial Medicine
Inflamm-aging: the missing link to COVID-19 age-related mortality?
The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289226/
“The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of “inflamm-aging”, mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.”
Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome
https://www.sciencedirect.com/science/article/pii/S1201971220307323
Inflammaging in general
Se https://en.wikipedia.org/wiki/Inflammaging
Inflamm-aging (also known as inflammaging or inflamm-ageing) is a chronic low-grade inflammation that develops with advanced age. It is believed to accelerate the process of biological aging and to worsen many age-related diseases.
Inflammaging is defined as low-grade chronic systemic inflammation established during physiological aging. Altered levels of proinflammatory cytokines (e.g., IL-6 and TNF-α), acute-phase reactants (C-reactive protein [CRP]), and decreases in IL-10 impair the maintenance of immunological homeostasis. Can Exercise Be an Immunotherapy? https://www.medscape.com/viewarticle/809935_7
An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963991/
“Liksom immunsvaret har inflammation en fysiologisk funktion i den normala kroppen. Måttliga inflammatoriska svar är fördelaktigt för kroppen men när överdriven, blir svaret skadligt. Förändringar i det inflammatoriska cytokinnätverket styr riktningen för inflammationsutvecklingen. Den dynamiska balansen i nätverket av proinflammatory cytokiner och antiinflammatoriska cytokiner upprätthåller den fysiologiska funktionen av inflammation i den normala kroppen. Tippa balansen från anti-inflammation till proinflammation kan leda till patologiska förändringar. Ihållande inflammation under inflamm-åldrandet kan orsaka inflammationsrelaterade sjukdomar.
Inflamm-åldrande är en avgörande faktor för åldrandets hastighet och av livslängd och är starkt relaterat till Alzheimers sjukdom [2], Parkinsons sjukdom, akut lateral skleros, multipel skleros, åderförkalkning, hjärtsjukdomar, åldersrelaterad makuladegeneration [14], diabetes typ II [15], osteoporos och insulinresistens [16], cancer, och andra sjukdomar. Inflamm-åldrande ökar också sjuklighet och dödlighet, avsevärt skadar hälsan hos patienter, och orsakar en nedgång i livskvaliteten för patienter [16]. Kronisk, subklinisk inflammation och immunsjukdomar samexisterar i processen för inflamm-åldrande. Epidemiologiska studier visar att med åldern finns det en obalans i förlusten av gammalt ben och bildandet av nytt ben. Inflamm-åldrande kan vara en av de bidragande faktorerna till obalansen och till den efterföljande överdriven förlust av ben. Inflammatoriska markörer av inflamm-åldrande ge kliniker med nödvändiga data för riskbedömning av osteoporos. Inflammatoriska cytokiner kan vara terapeutiska mål för att förbättra bildandet av ben hos äldre efter benoperationer [16]. Överdriven inflammation under inflamm-åldrande ökar sjuklighet och dödlighet hos patienter efter ben operationer, även om mekanismen för detta fortfarande oklart [17]. I processen för inflamm-åldrande, de patofysiologiska förändringar i tjocktarmen avslöjas på cell- och molekylära nivåer, och dessa kulminerar i inflammationen som leder till skada av magslemhinnan och epitel samt en minskning av epitels förmåga att regenerera [18] (figur 1).
Inflammaging: a new immune–metabolic viewpoint for age-related diseases – https://www.nature.com/articles/s41574-018-0059-4
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146930/
NB Unique form of chronic sinusitis in older patients https://www.sciencedaily.com/releases/2019/01/190123105817.htm
“With an initial goal of identifying subgroups of patients based on their inflammatory signature — the different cytokines and inflammatory proteins found in tissue or mucus — Vanderbilt investigators recognized that one of the identified subgroups was enriched in patients over age 60 “.
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence 2006
https://nyaspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1749-6632.2000.tb06651.x
“Abstract: In this paper we extend the “network theory of aging,” and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as “inflamm‐aging,” is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age‐related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ‐specific age‐related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer’s disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.”
Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition https://www.sciencedirect.com/science/article/pii/S156816371730003X
…”We conclude that slowing, controlling or reversing Low Grade Inflammation (LGI) is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted.”
Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity https://link.springer.com/article/10.1007/s00005-015-0377-3 –
Immune Senescence and Inflammaging Mini-Review https://www.bio-rad-antibodies.com/immune-aging-senescence.html
Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome https://www.frontiersin.org/articles/10.3389/fncel.2019.00353/full
“Fibromyalgia Syndrome (FMS) is a disorder of chronic, generalized muscular pain, accompanied by sleep disturbances, fatigue and cognitive dysfunction. There is no definitive pathogenesis except for altered central pain pathways. We previously reported increased serum levels of the neuropeptides substance P (SP) and its structural analogue hemokinin-1 (HK-1) together with the pro-inflammatory cytokines IL-6 and TNF in FMS patients as compared to sedentary controls. We hypothesize that thalamic mast cells contribute to inflammation and pain, by releasing neuro-sensitizing molecules that include histamine, IL-1β, IL-6 and TNF, as well as calcitonin-gene related peptide (CGRP), HK-1 and SP. These molecules could either stimulate thalamic nociceptive neurons directly, or via stimulation of microglia in the diencephalon. As a result, inhibiting mast cell stimulation could be used as a novel approach for reducing pain and the symptoms of FMS”.
https://www.mdpi.com/2073-4409/9/7/1565/htm Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids
Mast Cells (Part 3): The Mast Cell-Glia Interaction In Chronic Inflammation
The more inflammation happens, the more that mast cells and glia communicate and create stronger bonds/crosstalk.
https://mybiohack.com/blog/mast-cells-glia-sali-cirs
Immunosenescence, Inflammaging, and Their Implications for Cancer and Anemia https://link.springer.com/chapter/10.1007/978-981-13-3585-3_14
Special Issue ”Inflammaging and Oxidative Stress in Aging and Age-Related Disorders”
https://www.mdpi.com/journal/ijms/special_issues/inflammaging_oxidative_stress
The interplay between immunosenescence and age-related diseases https://link.springer.com/article/10.1007/s00281-020-00806-z
Aging is a major risk factor for the higher incidence and prevalence of chronic conditions, such as cardiovascular diseases, metabolic diseases, and neurodegenerative diseases. Chronic systemic sterile inflammation is crucially involved with the etiology and progression of these conditions [1]. Several features of premature aging have been reported in young adults or adults with these chronic conditions (Fig. 1). In the elderly, these conditions are often presented with multimorbidity and may finally lead to organ failure and death. With the advance of immunosenescence (aging of the immune system), older adults also become more susceptible to infectious diseases and cancer. Elderly population is at increased risk for developing and dying from influenza and coronavirus disease 2019 (COVID-19). Of note, the adults with chronic (inflammatory) conditions are the ones with heightened risk for developing severe COVID-19 and dying [2]. Therefore, there is an interplay between immunosenescence and age-related diseases. In this way, it is important to intervene more quickly and multidimensionally with novel preventive and therapeutic approaches. The study of immunosenescence can bring viable solutions for the prevention and treatment of these diseases as well as to increase the healthspan of elderly populations.
Multiple mechanisms of accelerated aging are similarly found in age-related diseases. Abbreviations: CMV, cytomegalovirus; SASP, senescence-associated secretory phenotype
Inflammaging and healring dysfunctions
Resolution of Inflammation (including Inflammageing) and Age-Related Hearing Loss (ARHL)
https://www.frontiersin.org/articles/10.3389/fncel.2017.00192/full – https://escholarship.org/content/qt45h1k38c/qt45h1k38c_noSplash_5fcccc3f6510d1bfd6388b48ff30fee7.pdf
“Another key contributor to several age-related diseases, including ARHL, is the state of chronic inflammation in the elderly known as ‘‘inflammaging’’ (Capri et al., 2006; Hunt et al.,
2010; Leng et al., 2011; Baylis et al., 2013; Verschuur et al., 2014). Inflammaging is a consequence of immune-senescence, the aging of the immune system (Capri et al., 2006; Hunt et al., 2010).
A potential link with inflammaging may be very important for ARHL, providing new approaches to prevent the development of this condition.
As a matter of fact, ARHL severity has already been linked to some factors associated with inflammation and inflammaging (Gates et al., 1993; Gates and Mills, 2005; Frisina et al., 2006;
Verschuur et al., 2014). For instance, it has been shown that spiral ganglion cell damage can be caused by changes in the immune system (Iwai et al., 2003, 2008), while vascular and metabolic changes may affect the stria vascularis and, indirectly, cause inflammatory damage (Saitoh et al., 1995; Ohlemiller, 2009; Fetoni et al., 2011). In a clinical trial an association was found between serum immunoglobulin G and hearing loss in individuals over 60 years of age (Lasisi et al., 2011). Thus, there is a high probability that inflammation and inflammaging could play a role in ARHL.”