Inflammaging

"[5] The secretome of senescent mesenchymal stem and stromal cells (MSCs) exhibits immunomodulatory effects and serves as a driver in inflammaging-related diseases.

The inflammasome is a multi-protein complex consisting of a sensor, an adapter, and an effector, that when activated, modulates caspases which cleave cytokines and result in an inflammatory signaling response.

[14] These various self, non-self, and quasi self molecules are recognized by receptors of innate immune cells, whose promiscuity allows for many different signals to lead to activation and consequently to inflammation.

In addition to inflammasome activation, with age, cellular components accumulate reactive oxygen species (ROS).

[16] Senescent cell populations increase with age and secrete a pro-inflammatory cocktail of chemicals, a condition known as senescence-associated secretory phenotype (SASP).

This is an essential process for cellular housekeeping that prevents protein aggregation and accumulation of damaged mitochondria that produce large quantities of reactive oxygen species.

As inflammasome precision declines with age, these aggregates, normally degraded, can be recognizes as a pathogen and lead to an inflammatory response.

Other possible factors that may lead to inflamm-aging include insufficient sleep, overnutrition, sensory overload, physical inactivity, altered gut microbiome, impaired intestinal epithelial barrier, and chronic stress occurring in any stage of the individual's life.

[2] Currently, levels of TNFa, IL-6 and IL-1 can be used as inflammatory biomarkers that indicate frailty, an altered immune system, functional decline and mortality associated with inflammaging .

[27] Additionally, elevated TNF-alpha levels are associated with increased systemic inflammation and contribute to inflammatory diseases like rheumatoid arthritis.

This explains post prandial inflammation, which involves innate immune system activation after ingesting a meal.

[29] In current times, natural selection does not favor those who are spared from inflammaging, as this occurs at ages past the reproduction window.

[30] Chronic inflammation and immunosenescence, which both increase with advanced chronological age, renders the elderly population more vulnerable to adverse, long term effects of viral infection by SARS-CoV2.

[31] This is corroborated with evidence demonstrating that SARS-CoV2 was present in cerebral spinal fluid of infected patients which displayed severe neurological symptoms.

While aging is the most significant risk factor in the development of neurodegenerative diseases like Alzheimers, Parkinson's, and Amyotrophic lateral sclerosis, chronic, low-grade inflammation and immunosenescence may be aggravated by a viral infection, worsening the aging phenotype and contributing to the development of neurodegenerative disease.

[31] Inflammaging and COVID-19 infection may lead to worse outcomes and contribute to the development of neurodegenerative disease in aged individuals.