Chronic Inflammation (Inflammaging)

Chronic inflammation, often referred to as inflammaging, is recognized as a significant hallmark of aging. It is characterized by a low-grade, chronic, systemic inflammation that persists throughout the aging process. Unlike acute inflammation, which is a necessary and beneficial process for fighting infections and healing injuries, chronic inflammation can have detrimental effects over time, contributing to the pathogenesis of various age-related diseases.

The Basis of Inflammaging

Inflammaging is driven by several factors, including:

• Cellular Senescence: Senescent cells accumulate with age and secrete inflammatory cytokines, chemokines, and proteases, known collectively as the senescence-associated secretory phenotype (SASP). This contributes significantly to the chronic inflammatory state.
• Immune System Dysregulation: Aging is associated with changes in the immune system, a phenomenon known as immunosenescence, which can lead to an imbalanced immune response and prolonged inflammatory activity.
• Genetic Factors: Certain genetic predispositions can influence the extent and impact of inflammaging.
• Environmental and Lifestyle Factors: Diet, lifestyle, and exposure to environmental toxins can contribute to or exacerbate chronic inflammation.

Impact on Health and Disease

Chronic inflammation is implicated in a wide range of age-related conditions, including:

• Cardiovascular Diseases: Chronic inflammation contributes to the development of atherosclerosis, hypertension, and other cardiovascular conditions.
• Metabolic Disorders: Inflammation is a critical factor in the pathogenesis of insulin resistance, type 2 diabetes, and metabolic syndrome.
• Neurodegenerative Disorders: Inflammatory processes are involved in the progression of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders.
• Cancer: Chronic inflammation can lead to DNA damage, promote tumor growth, and suppress immune surveillance.
• Musculoskeletal Disorders: Conditions like osteoarthritis and sarcopenia are associated with increased inflammatory activity.

Mechanisms of Inflammaging

Inflammaging involves various cellular and molecular pathways:

• Nuclear Factor-kappa B (NF-κB) Pathway: NF-κB is a key regulator of inflammatory responses. Its persistent activation is a common feature of chronic inflammation and aging.
• Inflammasomes: Inflammasomes are protein complexes that promote the production of pro-inflammatory cytokines such as IL-1β and IL-18, contributing to the chronic inflammatory milieu.
• Dysbiosis: Alterations in the gut microbiome can lead to increased intestinal permeability and a chronic systemic inflammatory state.
• Mitochondrial Dysfunction: Dysfunctional mitochondria can release reactive oxygen species and other signals that promote inflammatory responses.

Therapeutic Strategies

Several strategies are being investigated to mitigate inflammaging and its impact on age-related diseases:

• Anti-Inflammatory Drugs: Non-steroidal anti-inflammatory drugs (NSAIDs) and targeted biologics are used to reduce inflammation, although their long-term use in aging populations needs careful consideration due to side effects.
• Senolytics: Drugs that selectively eliminate senescent cells are being developed to reduce the burden of SASP and its inflammatory effects.
• Lifestyle Interventions: Diet, exercise, and stress management have been shown to influence inflammation levels and can be part of a comprehensive approach to reduce inflammaging.
• Immunomodulation: Strategies to modulate the immune system, including vaccines and immune-boosting therapies, are under investigation to address immunosenescence and chronic inflammation.

See Also

• Hallmarks of Aging
• Wikipedia - Chronic inflammation