Aging of the Immune System. Mechanisms and Therapeutic Targets

Abstract

Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…Vertebrates also have a hypothalamo‐pituitary axis, which is critical for neuro‐endocrine signaling during aging (Veldhuis, 2008). Unlike invertebrates, which rely on an innate immune system, vertebrates have also evolved an adaptive immune system, which plays roles in vertebrate aging in many aspects such as “immunosenescence” (gradual deterioration of the immune system during aging; Weng, 2006; Weyand & Goronzy, 2016) and “inflammaging” (chronic inflammation that occurs during aging; Monti, Ostan, Borelli, Castellani & Franceschi, 2016). Furthermore, aging in vertebrates is often accompanied by the development of cancers (Campisi, 2013), perhaps due to the presence of tissue‐specific stem cells which are more at risk for tumor‐inducing mutation (Batlle & Clevers, 2017).…”

Young and elderly oral squamous cell carcinoma patients present similar angiogenic profile and predominance of M2 macrophages: Comparative immunohistochemical study

“…The release of interleukin (IL)‐1, IL‐4, IL‐6, IL‐8, and IL‐10 by tumor cells participate in macrophage reprogramming for an M2‐phenotype, which produces anti‐inflammatory, protumor, and proangiogenic cytokines favoring proliferation of malignant cells, invasiveness and metastasis . Activation of M2‐polarized macrophages also influences lymphocyte subtypes, inhibiting cytotoxic T‐cells and stimulating regulatory T‐cells (Tregs), as well as Th2, eosinophils, basophils and mast cells …”

“…of M2-polarized macrophages also influences lymphocyte subtypes, inhibiting cytotoxic T-cells and stimulating regulatory T-cells (Tregs), as well as Th2, eosinophils, basophils and mast cells. 54,55 Among the studies assessing the age-related OSCC profile, few evaluate the role and functioning of the stromal cells in the tumor microenvironment. 5,7,13,19 By considering inflammatory cells, TAMs exhibiting M2 phenotype are often detected, being known its role in tumor progression and invasion capacity, increased tumor cell motility, persistent tumor growth, proangiogenic properties, and suppression of antitumor response.…”

COVID-19 — Toward a comprehensive understanding of the disease

“…Environmental factors can exaggerate these features into a level which is a danger to survival. For example, so-called immune risk phenotype (IRP) is never seen in centenarians as its burden does not allow the elderly to fight effectively with infections, and they die earlier [33,34]. Although many environmental factors affect the immune system, some of them notoriously deteriorate immunity (Table 1).…”