From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity

Abstract

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function. Subsequent scrutiny of chronic inflammation, or “inflammaging,” highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections. In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.

Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation

“…Generally, aging of the immune system is associated with a chronic low-grade inflammatory state, commonly referred to as inflammaging ( Figure 1C ), which is characterized by elevated levels of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α ( 45 , 61 ). This inflammatory imbalance may disrupt immune homeostasis and contribute to age-related pathologies, including neurodegeneration, cardiovascular and autoimmune disorders ( 8 , 62 , 63 ). Cellular senescence, characterized by irreversible growth arrest and altered secretory phenotype, contributes to immunosenescence by promoting chronic inflammation and tissue damage.…”

Pós COVID na Atenção Primária à Saúde e Ambulatorial Especializada: Reunindo evidências para o Sistema Único de Saúde e à Plataforma Clínica Global da OMS

“…Um dos fatores que parecem contribuir para a COVID longa é a idade. É importante observar que existe um remodelamento dependente da idade do sistema imune, chamado imunosenescência (58,59). Tal processo está associado a uma inflamação de baixo grau crônica e sistêmica, inclusive no SNC.…”

“…Tal processo está associado a uma inflamação de baixo grau crônica e sistêmica, inclusive no SNC. Evidências têm mostrado que citocinas inflamatórias induzem significativas desregulações funcionais, incluindo neurogênese, transmissão e plasticidade sináptica, função mitocondrial e homeostase cerebral (59), que podem acelerar a progressão de várias doenças neurodegenerativas e transtornos neuropsiquiátricos. A neuroinflamação associada ao envelhecimento também tem sido sugerida como um fator de suscetibilidade do SNC à tempestade de citocinas na COVID-19 (60).…”

Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease

“…As individuals age, changes in immune regulation mechanisms can lead to a breakdown of self-tolerance, resulting in autoimmune reactions [6,68]. The interplay between immunosenescence and autoimmunity has implications for the development of autoimmune disorders in older populations [6,46,69,70]. Diseases like rheumatoid arthritis, systemic lupus erythematosus, and autoimmune thyroid diseases are more prevalent in elderly individuals, and immunosenescence is believed to contribute to these conditions [71].…”