The best Vitamin supplements designed for Heart
Browsing for state-of-the-art authorised quality health products? Discover about these beneficial Medically Approved Vitamins.
Accumulation of lingering senescent cells is an important mechanism of aging, as these errant cells secrete a potent mix of molecules that spurs chronic inflammation and degrades nearby tissue structure and function. Evidence has emerged for the presence of senescent supporting cells in the brain, such as microglia and astrocytes, to contribute to many different neurodegenerative diseases. Animal studies in which first generation senolytic drugs are used to clear senescent cells from the brain have show that such treatments are capable of reversing some forms of neurodegenerative pathology, such as the neuroinflammation and tau aggregation characteristic of tauopathies.
In today's open access paper, the authors report on an assessment of the numbers of what they term dystrophic microglia in human brains, cells that are most likely senescent but not conclusively determined to be so. They find that the numbers of these dystrophic cells are elevated in neurodegenerative conditions when compared to similarly aged controls without clear neurodegenerative disease. Aging progresses at a somewhat different pace from individual to individual, and differences in the burden of senescent cells - perhaps due to exposure to pathogens in the case of microglia and other immune cells - may be an important determinant of differences in the rate of aging and risk of age-related disease.
Inflammation and cellular senescence are hallmarks of aging. Almost two decades ago, dystrophic microglia were described with beading and fragmentation of the branches of the microglia. In contrast to the hypertrophic microglia often seen following central nervous system injury, the dystrophic microglia were proposed to be a form of microglia senescence. While there is no single specific marker of cellular senescence, a handful of markers, such as p16INK4a, have some affinity for identifying senescent cells. Using a p16INK4a approach to target the removal of senescent cells in a mouse model of tauopathy resulted in reduced tau pathology, neuronal degeneration, and cognitive deficits. Given the necessary cellular stressors, microglia can become senescent/dystrophic.
Throughout the body, cellular senescence is associated with the secretion of inflammatory mediators, defined as the senescence-associated secretory phenotype. Even a small number of senescent cells in any organ can contribute to disease and by the spread of the senescence phenotype to neighboring healthy cells. The hypothesis that dystrophic microglia is an age-associated microglia morphology has not been experimentally tested. While cellular senescence generally increases with age, it can occur at any stage of life in response to stressors. This led our first question: are dystrophic microglia associated with chronological age in people? We hypothesized that with increasing years, there would be an increasing proportion of dystrophic microglia. Previous work, including our own, has found dystrophic microglia in aged humans without neurodegenerative pathology.
In contrast to the view that dystrophic microglia are purely an age-related change in microglial morphology, there is compelling evidence that dystrophic microglia are more closely associated with neurodegenerative disease. Previous studies identified dystrophic microglia in people with age-related neurodegenerative disease, including Alzheimer's disease (AD). These findings lead to our second question: is increased dystrophic microglia a disease associated phenomenon? We hypothesized that the absolute numbers, and/or percentage of dystrophic microglia, would be greater in people with neurodegenerative disease than age-matched controls.
To address these questions, we studied brains from the University of Kentucky Department of Pathology and the UK-ADRC biobank, covering the adult lifespan from 10-90+ years of age. Stereological counts of the total number of microglia, number of hypertrophic microglia, and the number of dystrophic microglia were conducted in 3 brain regions: hippocampal CA1, frontal cortex, gray matter, and white matter. We found that in the absence of neurodegenerative disease, there was only a modest increase in dystrophic microglia with age. However, with neurodegenerative pathology, the percentage of microglia observed to be dystrophic was much greater than aged-matched controls.
Have a look at Nitric Oxide and Cardiovascular fitness.
source https://www.fightaging.org/archives/2021/01/senescent-microglia-are-present-in-greater-numbers-in-the-brains-of-patients-with-neurodegenerative-conditions/
No comments:
Post a Comment