Abstract
As a consequence of the considerable increase in the human lifespan over the last century, we are experiencing the appearance and impact of new age-related diseases. The causal relationships between aging and an enhanced susceptibility of suffering from a broad spectrum of diseases need to be better understood. However, one specific shared feature seems to be of capital relevance for most of these conditions: the low-grade chronic inflammatory state inherently associated with aging, i.e., inflammaging. Here, we review the molecular and cellular mechanisms that link aging and inflammaging, focusing on the role of the innate immunity and more concretely on the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, as well as how the chronic activation of this inflammasome has a detrimental effect on different age-related disorders.
Highlights
Aging is a natural and unavoidable process that entails the progressive accumulation of changes over time that are typically associated with an increased susceptibility to several conditions of different natures, such as cardiovascular, metabolic, or neurodegenerative disorders
Inflammatory cytokines promote a chronic state of low-grade inflammation known as “inflammaging,” which is independent from the pathogen-mediated activation of immune cells
These conditions present a higher incidence in the elderly population; NLRP3 appears as a shared therapeutic target for inflammaging and age-related diseases
Summary
Aging is a natural and unavoidable process that entails the progressive accumulation of changes over time that are typically associated with an increased susceptibility to several conditions of different natures, such as cardiovascular, metabolic, or neurodegenerative disorders. Cell senescence is triggered by some of the mechanisms and molecules inherent to aging, e.g., telomere shortening, increased oxidative stress, and inflammatory cytokines. Cells 2020, 9, 1552 inflammasome is involved in a broad spectrum of disorders including but not limited to autoimmune diseases, type-2 diabetes, and neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). These conditions present a higher incidence in the elderly population; NLRP3 appears as a shared therapeutic target for inflammaging and age-related diseases. We provide a global vision of the implications of the innate immunity in the aging process, stressing the role of the NLRP3 inflammasome in aged-related metabolic and neurodegenerative conditions
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