Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

Abstract

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored.

Keywords: COPD; cancer; cardiovascular disease; diabetes; neurodegenerative disease; reactive oxygen species; rheumatoid arthritis.

Figure 1

Schematic summarizing the molecular mechanisms contributing to CVD progression. CCL-2, chemokine (C-C motif) ligand 2; CVD, cardiovascular disease; EGFR, epidermal growth factor receptor; LDL, low density lipoprotein; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; NOX, NADPH oxidase; ROS, reactive oxygen species; SIRT1, sirtuin-1; SOD, superoxide dismutase; XO, xanthine oxidase.

Figure 2

Schematic summarizing the molecular mechanisms contributing to cancer progression. EGFR, epidermal growth factor receptor; IL-1, interleukin-1; IL-6, interleukin-6; MAPK/ERK, mitogen-activated protein kinase/extracellular regulated protein kinases; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; NOX1, NADPH oxidase 1; PFK, phosphofructokinase; PI3K/AKT, phosphatidyl inositol 3-kinase/protein kinase B; PPP, pentose phosphate pathway; ROS, reactive oxygen species; SIRT1, sirtuin-1; STAT3, signal transducers and activators of transcription 3; TNF-α, tumor necrosis factor-α.

Figure 3

Schematic showing the molecular mechanisms underlying Alzheimer’s disease (A) and Parkinson’s disease (B). AD, Alzheimer’s disease; Aβ, amyloid beta plaques; BBB, blood brain barrier; CNS, central nervous system; JNK/p38 MAPK, c-Jun N-terminal kinase/p38 mitogen-activated protein kinase; MMP9, matrix metalloprotease 9; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; PD, Parkinson’s disease; ROS, reactive oxygen species; SIRT1, sirtuin-1.

Figure 4

Schematic showing the molecular mechanisms contributing to COPD progression. COPD, chronic obstructive pulmonary disease; IL-17A, interleukin-17A; IL-21, interleukin-21; MMP9, matrix metalloprotease 9; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; PGC, peroxisome proliferator-activated receptor-γ coactivator; ROS, reactive oxygen species; SIRT1, sirtuin-1; STAT3, signal transducers and activators of transcription 3; TLR, toll-like receptor.

Figure 5

Schematic showing the molecular mechanisms contributing to diabetes progression. IL-1β, interleukin-1β; IL-8, interleukin-8, IL-6, interleukin-6; IRS1, insulin receptor substrate 1; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.

Figure 6

Schematic summarizing the molecular pathways contributing to RA. COX-2, cyclo-oxygenase 2; CPC, circulating progenitor cells; GSH, glutathione; IFN-γ, interferon-γ; iNOS, inducible nitric oxide synthase; IL-1β, interleukin-1β; RA, rheumatoid arthritis; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.

Figure 7

Schematic summarizing the primary molecular signaling involved in different diseases including CVD, cancer, AD, PD, COPD, diabetes, and RA. AD, Alzheimer’s disease; Aβ, amyloid beta plaques; BBB, blood brain barrier; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; IL-1, interleukin-1; IL-6, interleukin-6; JNK/p38 MAPK, c-Jun N-terminal kinase/p38 mitogen-activated protein kinase; LDL, low density lipoprotein; MMP9, matrix metalloprotease 9; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B; SIRT1, sirtuin-1; PD, Parkinson’s disease; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.