Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock

Abstract

Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological reserve in response to stress. Ageing is closely related to oxidative damage and involves immunosenescence and tissue impairment or metabolic imbalances that trigger inflammation and inflammasome formation. One of the main ageing-related alterations is the dysregulation of the immune response, which results in chronic low-level, systemic inflammation, termed “inflammaging”. Genetic and epigenetic changes, as well as environmental factors, promote and/or modulate the mechanisms of ageing at the molecular, cellular, organ, and system levels. Most of these mechanisms are characterized by time-dependent patterns of variation driven by the biological clock. In this review, we describe the involvement of ageing-related processes with inflammation in relation to the functioning of the biological clock and the mechanisms operating this intricate interaction.

The role of circadian clock in regulating cell functions: implications for diseases

“… 4 Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24‐h rhythm, thus generating the rhythmicity of various cellular immune functions 63 . These cell‐autonomous rhythms encompass cytokine production, trafficking, and phagocytosis 64,65 . A wide range of immune cells including macrophages, neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and lymphocytes (B cells, T cells, and innate lymphoid cell [ILCs]) in diverse tissues are under the control of circadian clock (Figure 2).…”

“… 63 These cell‐autonomous rhythms encompass cytokine production, trafficking, and phagocytosis. 64 , 65 A wide range of immune cells including macrophages, neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and lymphocytes (B cells, T cells, and innate lymphoid cell [ILCs]) in diverse tissues are under the control of circadian clock (Figure 2 ). Circadian regulation of immune activity involves the daily fluctuation of circulating leukocyte counts, levels of secreted cytokines, tissue infiltration of immune cells, innate and adaptive immune responses, and inflammatory signaling pathways (Figure 2 ).…”

The Influence of Antioxidants on Oxidative Stress-Induced Vascular Aging in Obesity

“…For example, a high-fat diet in obese individuals can change circadian clock genes [ 105 ]. On the other hand, circadian clocks are involved in metabolic health, regulation of antioxidant levels, mitochondrial dynamics, ROS production, aging, and adipose tissue remodeling [ 97 , 105 , 106 , 107 , 108 ].…”

Senescent T cells: Beneficial and detrimental roles

“…106 The question is whether the expanded CMV-specific effector CD8 + T cells that are found in older subjects 28,101 have an impact on health span. Since aging and increased low-grade systemic inflammation are linked, 76,107 the expanded population of end-stage (senescent)…”

“… 106 The question is whether the expanded CMV‐specific effector CD8 + T cells that are found in older subjects 28 , 101 have an impact on health span. Since aging and increased low‐grade systemic inflammation are linked, 76 , 107 the expanded population of end‐stage (senescent) CMV‐specific CD8 + T cells as well as CD4 + CTL that may express NK receptors can target healthy tissues expressing NK ligands as a result of inflammageing; this process may trigger chronic nonspecific tissue damage.…”