Chronic inflammation is a persistent state of low-grade inflammation that occurs when the immune system is dysregulated and produces excessive pro-inflammatory factors. Chronic inflammation is associated with many age-related diseases, such as cardiovascular disease, diabetes, cancer, and neurodegenerative disorders. In fact, chronic inflammation has been proposed as a new hallmark of aging, along with other features such as genomic instability, telomere attrition, and cellular senescence (López-Otín et al., 2013).
Chronic inflammation can be caused by various factors, such as genetic predisposition, environmental exposure, lifestyle habits, and microbial infections. Some of these factors can trigger a process called inflammaging, which is the gradual accumulation of pro-inflammatory factors in the body over time.
Inflammaging is influenced by both intrinsic and extrinsic factors, such as immunosenescence (the decline of immune function with age), oxidative stress (the imbalance between free radicals and antioxidants), mitochondrial dysfunction (the impairment of cellular energy production), and chronic stimulation by pathogens or endogenous molecules (such as damaged DNA or proteins) (Franceschi et al., 2000).
Inflammaging can have detrimental effects on various tissues and organs, such as the brain, the heart, the liver, the kidneys, the skin, and the joints. Inflammaging can impair the function and structure of these organs by inducing oxidative damage, fibrosis, apoptosis, necrosis, or autophagy (the self-degradation of cellular components).
Inflammaging can also affect the communication and interaction between different organs and systems, such as the endocrine system (the regulation of hormones), the nervous system (the transmission of signals), and the microbiome (the collection of microorganisms in the gut) (Xia et al., 2016).
Inflammaging can also modulate the epigenetic landscape of cells, which is the set of chemical modifications that regulate gene expression without altering the DNA sequence. Inflammaging can alter the methylation (the addition or removal of methyl groups) or acetylation (the addition or removal of acetyl groups) of histones (the proteins that wrap around DNA) or DNA itself.
These epigenetic changes can affect the expression of genes involved in inflammation, aging, and disease. For example, inflammaging can increase the expression of pro-inflammatory genes such as TNF-α or IL-6, or decrease the expression of anti-inflammatory genes such as IL-10 or TGF-β. Inflammaging can also affect the expression of genes involved in cellular senescence (the irreversible arrest of cell division), such as p16 or p21, which can contribute to tissue dysfunction and degeneration (Lavin et al., 2019).
Therefore, chronic inflammation is a major factor that drives aging and age-related diseases. However, chronic inflammation can be modulated by various interventions, such as diet, exercise, pharmacology, or gene therapy.
These interventions can target different aspects of chronic inflammation, such as reducing pro-inflammatory factors, enhancing anti-inflammatory factors, restoring immune balance, improving mitochondrial function, repairing oxidative damage, removing senescent cells, or reversing epigenetic alterations. These interventions can potentially delay or prevent the onset of age-related diseases and extend healthspan and lifespan (Fontana et al., 2019).
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