Molecular Inflammation as an Underlying Mechanism of the Aging Process and Age-related Diseases

Abstract

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Functional Differences In Gingival Fibroblasts Obtained from Young and Elderly Individuals

“…The data obtained in this study were corroborated by Chung et al (18), who also demonstrated increased synthesis of NO related to inflammatory responses against cell aging. These authors reported that the largest increase in activation of the NFκB pathway also promoted a rise in some inflammatory cytokine synthesis, such as TNF-α, interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and cyclooxygenase-2 (COX-2), leading to inflammatory diseases in the elderly.…”

“…The presence of inflammation in tissues with high concentrations of chemokines and inflammatory mediators induces the generation of reactive oxygen species (ROS) by various cells (17,18). At low concentrations, ROS can accelerate the repair process; however, at higher concentrations or prolonged exposure, ROS can cause tissue damage by lipid peroxidation in different organelles, such as the cell membranes (17).…”

“…Moreover, during the aging process the cells undergo phenotypic changes and respond differently, mainly towards molecules of the inflammatory process (18).…”

Early childhood poverty, immune-mediated disease processes, and adult productivity

“…Physical aging, for example, is thought to be related, in part, to the long-term accumulation of damage from repeated episodes of acute inflammation (31). Inflammatory changes are also an integral part of the human stress response and have been linked to the development of a broad range of adversity-related chronic diseases, such as coronary heart disease, asthma, and hypertension (6,7,13,32), and conditions of aging (33,34). Although such morbidities are likely to have multiple and interactive etiologic pathways [e.g., for hypertension (35)], immune-mediated processes have been increasingly implicated in their pathogenesis.…”

Gingival Wound Healing

“…However, a prolonged inflammatory response may delay wound healing and probably favor tissue fibrosis, reducing the chances of true regeneration (Pacios et al 2012;Arancibia et al 2013). It is important to consider that several studies have documented that aging cells and tissues show increased levels of inflammation (Chung et al 2011). …”