lncRNA-Triggered Macrophage Inflammaging Deteriorates Age-Related Diseases

Abstract

Aging and age-related diseases (ARDs) share basic mechanisms largely involving inflammation. A chronic, low-grade, subclinical inflammation called inflammaging occurs during aging. Autophagy defects, oxidative stresses, senescence-associated secretory phenotypes (SASPs), and DNA damage generally contribute to inflammaging and are largely regulated by numerous lncRNA through two-level vicious cycles disrupting cellular homeostasis: (1) inflammaging and the cellular senescence cascade and (2) autophagy defects, oxidative stress, and the SASP cascade. SASPs and inflammasomes simultaneously cause inflammaging. This review discusses the involvement of macrophage inflammaging in various ARDs and its regulation via lncRNA. Among macrophages, this phenomenon potentially impairs its immunosurveillance and phagocytosis mechanisms, leading to decreased recognition and clearance of malignant and senescent cells. Moreover, SASPs extracellularly manifest to induce paracrine senescence. Macrophage senescence escalates to organ level malfunction, and the organism is more prone to ARDs. By targeting genes and proteins or functioning as competing endogenous RNA (ceRNA), lncRNA regulates different phenomena including inflammaging and ARDs. The detailed mechanism warrants further elucidation to obtain pathological evidence of ARDs and potential treatment approaches.

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

“…Several lncRNAs are found involved in miRNAs sponging activities as well in degenerative mechanisms, like in for instance lumbar intervertebral disc degeneration [ 162 ] or in age-related diseases (ARDs) where lncRNAs can affect many cellular homeostasis layers [ 163 ].…”

Intimate Relations—Mitochondria and Ageing

“…This is partly due to their loss of differentiated function, as they contribute to tissue mass without performing tissue specific roles. In addition, they release a complex pro-inflammatory mixture of cytokines, growth factors and enzymes (the senescence associated secretory phenotype, SASP) that can drive bystander cells into senescence and contribute to the damaging inflammation that accompanies ageing [ 319 , 320 , 321 , 322 , 323 , 324 ]—see Figure 9 .…”

Antioxidant stress and anticancer activity of peptide‑chelated selenium in vitro

“…Therefore, OS is associated with the occurrence and development of cancer. OS results in cell apoptosis/death, stressors alter micro (mi)RNA expression level profiles and miRNAs serve a role in the cell response to stress ( 38 ).…”

“…In addition, selenium nanoparticles loaded with anticancer molecules offer a novel strategy for cancer treatment ( 37 ). Moreover, lncRNAs regulate OS to maintain homeostasis ( 38 ).…”