Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

Abstract

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

Efficacy of Long-Term Feeding of α-Glycerophosphocholine for Aging-Related Phenomena in Old Mice

“…1). A number of studies have reported that aging decreases mRNA expressions of nerve growth factor, nitric oxide synthase, and long-term potentiation-related genes, and increases the expression of genes associated with NADPH oxidase and inflammation [26][27][28][29][30]. Our result demonstrated that mRNA expression levels of Gp91 phox and Mcp-1 were elevated with aging, while Ampa1 expression levels significantly declined (Fig.…”

Role of thymopoiesis and inflamm-aging in COVID-19 phenotype

“…2 Not surprisingly, a progressive propensity toward a proinflammatory phenotype, identified as inflamm-aging, plays a key role in the remodeling of the immune system at older ages, with evidence pointing to an inability to fine-control inflammation. 5 Thus, in our opinion, the role of the thymus could be crucial in the modulation of the immune response toward SARS-CoV-2 leading to a less severe phenotype in children when compared with those in adult COVID-19 patients. On the other hand, inflamm-aging associated with the absence of thymopoietic mechanisms could be a predisposing condition that sustains the cytokine release storm as is most often reported in adult COVID-19 subjects, especially in the older COVID-19 patients.…”

Emerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation

“…Aging is one of the major risk factors for MI, and monocytederived cardiac macrophages as well as granulocytes increase in numbers during aging while the overall macrophage population decreases (Molawi et al, 2014). Aging is also related to clonal hematopoiesis with a myeloid bias, an overall increased systemic inflammatory tone, dysregulation of soluble mediators including cytokines, chemokines, and growth factors all together reducing immune tolerance, a phenotype also described as ''inflamm-aging'' (Fuster et al, 2017;Jaiswal et al, 2017;Rea et al, 2018;Swirski, 2018). However, the overall impact of these age-related changes within the hematopoietic and the immune system on the onset of MI have not been quantified to detail yet and certainly need further clarification.…”