The conundrum of human immune system “senescence”

Pawelec, Graham; Bronikowski, Anne M.; Cunnane, Stephen C.; Ferrucci, Luigi; Franceschi, Claudio; Fülöp, Tamás; Gaudreau, Pierrette; Gladyshev, Vadim N.; Gonos, Efstathios S.; Gorbunova, Vera; Kennedy, Brian K.; Larbi, Anis; Lemaître, Jean François; Liu, Guang Hui; Maier, Andrea B.; Morais, José A.; Nóbrega, Otávio de Tolêdo; Moskalev, Alexey; Rikkert, Marcel G M Olde; Seluanov, Andrei; Senior, Alistair M.; Ukraintseva, Svetlana V.; Vanhaelen, Quentin; Witkowski, Jacek M.; Cohen, Alan A.

doi:10.1016/j.mad.2020.111357

Cited by 86 publications

(65 citation statements)

References 82 publications

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“…Immunosenescence of the innate immune system is characterized by reduced cellular superoxide production and capability for phagocytosis. The reduced naïveto-memory cell ratio and expansion of mature cell clones characterize immunosenescence of the acquired immune system [19,20]. Even if the precise and intricated mechanisms are still in exploration, many physiological phenomena have been proposed to explain the immune response remodeling over time, including chronic exposure to antigens, impaired telomerase activity, mitochondrial dysfunction, defective autophagy, endoplasmic reticulum stress, Fig.…”

Section: Importance Of the Patient's General Pre-infection Medical Conditionmentioning

confidence: 99%

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Post-COVID-19 acute sarcopenia: physiopathology and management

et al. 2021

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In this review, we discuss the pathophysiologic and management aspects of acute sarcopenia in relation to SARS-CoV-2 infection. COVID-19 is as a multi-organ infectious disease characterized by a severe inflammatory and highly catabolic status, influencing the deep changes in the body build, especially the amount, structure, and function of skeletal muscles which would amount to acutely developed sarcopenia. Acute sarcopenia may largely impact patients’ in-hospital prognosis as well as the vulnerability to the post-COVID-19 functional and physical deterioration. The individual outcome of the COVID-19 and the degree of muscle mass and functional loss may be influenced by multiple factors, including the patient’s general pre-infection medical and functional condition, especially in older adults. This paper gathers the information about how the SARS-CoV-2 hyper-inflammatory involvement exacerbates the immunosenescence process, enhances the endothelial damage, and due to mitochondrial dysfunction and autophagy, induces myofibrillar breakdown and muscle degradation. The aftermath of these acute and complex immunological SARS-CoV-2-related phenomena, augmented by anosmia, ageusia and altered microbiota may lead to decreased food intake and exacerbated catabolism. Moreover, the imposed physical inactivity, lock-down, quarantine or acute hospitalization with bedrest would intensify the acute sarcopenia process. All these deleterious mechanisms must be swiftly put to a check by a multidisciplinary approach including nutritional support, early physical as well cardio-pulmonary rehabilitation, and psychological support and cognitive training. The proposed holistic and early management of COVID-19 patients appears essential to minimize the disastrous functional outcomes of this disease and allow avoiding the long COVID-19 syndrome.

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Section: Importance Of the Patient's General Pre-infection Medical Conditionmentioning

confidence: 99%

“…IL-1, IL-6, TNF-α and CRP. Inflammaging is a part of a wider spectrum of immunosenescence [19,32]. Of the innate immune system, monocytes and macrophages are suggested to contribute to inflammaging more than any other cell type.…”

Section: The Sars-cov-2 Inflammatory Involvementmentioning

confidence: 99%

Post-COVID-19 acute sarcopenia: physiopathology and management

et al. 2021

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“…As argued in the consensus paper noted above [1] our knowledge of age-associated immune dysfunction and its clinical consequences specifically in people is limited, and relies to a great extent on extrapolation from animal models, especially mice -which are known to be quite different from humans [16]. Clearly, hematopoiesis may be so severely affected in the oldest old that it becomes essentially monoclonal, but what this means for immune status is not clear [17].…”

Section: Efficacy Of the Sars-cov-2 Spike Rna Vaccine Bnt162b In Oldementioning

confidence: 99%

“…Immunosenescence causes increased susceptibility and severity of infectious disease, poor responses to vaccination, and increased autoimmunity and canceror so the received wisdom as reflected in innumerable publications has it. The current paradigm as recently formulated during a consensus-seeking workshop [1] is that age-associated alterations to hematopoiesis result in a skewed output of immune cells to the periphery, with fewer lymphocytes and more myeloid cells. This paucity of T-cell precursors together with developmentally-programmed thymic involution results in markedly decreased generation of functional naïve T cells and contributes to a reduced T cell receptor repertoire, thus compromising the ability of the individual to respond to neoantigens.…”

Section: Introductionmentioning

confidence: 99%

Unanticipated efficacy of SARS-CoV-2 vaccination in older adults

Pawelec

McElhaney

2021

Immun Ageing

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The rapidity with which vaccines against COVID-19 have been developed and tested is unprecedented. As classically the case with randomized clinical trials, many studies excluded older adults. However, given the early realisation that senior citizens were most highly susceptible to COVID, older individuals have been included in licensing trials under these unusual conditions. The recently published results from the Comirnaty Vaccine (BNT162b) trial unexpectedly documented that vaccine efficacy was equally exceptionally high in older and younger adults. These extremely encouraging trial results with a neoantigen vaccine may suggest the beginning of a paradigm shift in our view of the impact of immunosenescence on vaccination against novel infectious diseases.

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“…In this study, antibody levels were the only measure of immune response. Considering the increasingly recognised importance of cell-mediated immunity in responses to viral infections, including SARS-CoV-2, in older adults, 6 future studies will ideally include assays of cell-mediated immunity to investigate whether patterns of protection vary between humoral and cell-mediated immunity. In order to understand immune responses and protection from severe outcomes and reinfection, the immune responses (humoral and cell-mediated immunity) and other host features of vulnerability to disease or resilience must be understood.…”

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confidence: 99%