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Chronic sterile inflammation with aging was termed by Claudio Franceschi “inflamm-aging”. The molecular mechanisms of the induction of inflammation and cellular senescence intersect through activation of the TLR/NF-κB, cGAS/STING/IFN 1,3, AGEs/RAGE molecular signaling pathways and the assembly of the NLRP3 inflammasome. Immunosenescence results in increased susceptibility and severity of infectious diseases and non-communicable age-associated diseases, among them cancer, cardio-vascular disease, and autoimmunity. 201-202.)įollowing a century of study, at the present time, natural immunity is understood to consist of three interrelated parts: physiological barriers, innate immunity and adaptive immunity. “Vvedenie v nauchnoe izuchenie starosti” (An introduction to the scientific study of aging), pp. It is a scientific question, like many others.” (Elie Metchnikoff, Etudy o Prirode Cheloveka (Etudes on the Nature of Man), The USSR Academy of Sciences Press, Moscow, 1961 (1903), Ch. I must point out to the reader from the beginning that this problem is not yet solved, but its solution does not involve anything impossible. Therefore, it would seem that the means to use in the struggle against pathological aging should be, on the one hand, the strengthening of the most valuable elements of the organism, and on the other, the attenuation of the aggressive onslaught of the phagocytes. the tissues of the muscle, kidney, lung, and brain) and phagocytes (“low/primitive elements”), and that the vitality of the former is, for the most part, diminished, whereas the latter, on the contrary, show increased activity. In Metchnikoff’s own words: “We saw that, during aging, there occurs a struggle between noble elements (parenchymal tissues, e.g. Metchnikoff was the author of arguably the first systematic scientific theory of aging, interrelating the processes of immunity and senescence (. Moreover, Metchnikoff can also be credited for the establishment of the interdisciplinary connection between these fields, in particular between aging research and immunology.
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Both the terms “gerontology” (“the study of aging”) and “thanatology” (“the study of death”) were coined by him in the “Etudes On the Nature of Man” published in 1903, which may mark the beginning of these scientific fields. Yet, he may also be well credited as “the father” of gerontology - the disciplinary term he coined. Metchnikoff is well recognized as a pioneering immunologist and microbiologist, a vice-director of the Pasteur Institute in Paris, and the Nobel Laureate in Physiology or Medicine of 1908 for the discovery of phagocytosis (a major contribution to the cellular theory of immunity). Historically, the field originated at the turn of the 20 th century with the work of Elie Metchnikoff whose 175 th anniversary we celebrated on (July 15, 1916). At this time, it is appropriate to review the current state of the science of innate and adaptive immunity in aging and longevity, as well as the historical origins of this field of study, to further promote the research in this area. The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which has stressed the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons.