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Immune System Aging and its Contribution to Cardiovascular Disease

Today's open access paper is a survey of the known ways in which the aged immune system contributes to disruption of function in the cardiovascular system. As the selected snippets illustrate, this is a relationship dominated by chronic inflammation. Raised and constant inflammation is characteristic of the systematic failure of the immune system in late life: it becomes both overactive and ineffective, and the consequent inflammation causes detrimental reactions in many important cell populations.

In the short term inflammation is useful, a necessary part of the response to infection and injury. When it runs without cease, however, the result is a loss of function in vital tissues - such as the vascular system - that ultimately proves fatal. For example, inflammation contributes to vascular stiffness by degrading the normal activities of smooth muscle cells. This causes hypertension, which in turn causes pressure damage to fragile tissue structures and accelerates the development of atherosclerosis. The combination of hypertension and atherosclerosis later results in the catastrophic rupture of a stroke or heart attack.

Thus repairing the contributing causes of immune aging is an important goal for our broader rejuvenation biotechnology community. If achieved, restoration of more youthful immune function will produce significant benefits, but it is by no means a simple task. It will require at least four distinct research and development programs. Firstly, replace the hematopoietic stem cell population in the bone marrow, responsible for generating immune cells, and dampen the harmful signaling that suppresses stem cell function in the old body. Secondly, restore the thymus to youthful size and function. The thymus is where T cells of the adaptive immune system mature, and its age-related atrophy greatly impacts the quality of the immune system. Thirdly, clear out the damaged and malfunctioning immune cells that accumulate over a lifetime, using some form of targeted cell-killing technology. Lastly restore the structure and function of the lymphatic system, used by immune cells to coordinate the immune response.

Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives

The pro-inflammatory drive observed with senescence, already defined as inflammaging, and the phenomenon of immunosenescence, which indicates an age-related decline in several immune functions, are multifactorial events of the older age. Growing evidence indicates that these events realize a self-perpetuating condition that favors the development of acute and chronic age-related diseases, spanning from increased susceptibility to infections, to cardiovascular (CV) and neurological diseases. CV diseases (CVD), in particular, are a leading cause of death even at older ages.

Viral infections are one of the triggers to DNA damage response activation. Herpes viruses exploit this mechanism to benefit their replication, thus providing a significant contribution to the accumulation of senescent cells that, in turn, facilitates the development of chronic age-related diseases. As an example, in a cohort of 511 individuals aged ≥65 years who were followed up for 18 years, cytomegalovirus (CMV) infection showed an association with increased mortality, reduced life expectancy by a magnitude of about 3.7 years, and a near doubling of CV deaths.

Recent evidence indicates intestinal microbial imbalance, i.e., dysbiosis, as another trigger to secondary sustained inflammatory responses related to the development of chronic/autoimmune diseases and cancer. A key feature of gut microbial changes with age is the reduced biodiversity, with increase in pathobionts and decreased health-promoting bacteria, such as bifidobacteria. This unbalance at the advantage of pathogenic microbial communities disrupts a fine mechanism of mucosal barrier integrity, where fermentation of starches and dietary fibers normally contributes to the production of mucus and lipid metabolites, such as short-chain fatty acids (acetate, propionate, butyrate), which modulate apoptosis and inflammation.

Functional and anatomical CV consequences of inflammaging/immunosenescence involve endothelial dysfunction and arterial stiffness, the principal mediators of vascular damage that translates into hypertension and atherosclerosis, leading contributors to CVD. Endothelial dysfunction is an early marker of vascular aging. With aging, oxidative and nitrative stress, as well as disruption of basic metabolic pathways, contribute to endothelial dysfunction. Activation of vascular smooth muscle cells (VSMCs) following inflammatory stimuli determines their phenotypic transition from the contractile to the synthetic phenotype, which allows their migration from the vascular media to the intima and increases their capacity to generate extracellular matrix proteins, with consequent arterial wall thickening.

Inflammation-stimulated VSMCs can also transdifferentiate into an osteoblastic phenotype, enabling mineralization and calcium deposition in the arterial media, while the activation of matrix metalloproteinases determines degradation of elastin and collagen of the vessel wall. All these mechanisms contribute to the phenomenon of arterial stiffness.

Comments

In the following paper they were able to increase thymus weight and immune function with an oyster extract.

"Oyster (Crassostrea gigas) Hydrolysates Produced on a Plant Scale Have Antitumor Activity and Immunostimulating Effects in BALB/c Mice"

"The relative weights of the spleen and thymus are important indices of nonspecific immunity. It was reported that oral administration of immunopotentiators increased the weights of spleens and thymuses in S180-bearing mice [29]. Our results showed that the relative weights of spleens and thymus increased significantly in a dose-dependent manner in the mice treated with oyster hydrolysates, suggesting that oyster hydrolysates probably function as an immunostimulator."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852837/

Posted by: Lee at December 4th, 2018 8:38 AM

The most interesting studies that I have read regarding immune system regeneration are those done by Valter Longo on 3-5 day water fasts.

Posted by: August at December 4th, 2018 9:38 PM

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