BHLHE40 and BHLHE41 Deletion May Make Macrophages and Microglia More Efficient

Macrophages in the body and microglia in the brain are similar forms of innate immune cell, responsible for clearing metabolic waste, among other duties. A number of age-related conditions involve the growing incapacity of macrophages or microglia, their transition to inflammatory states, and inability to clear debris and waste as they should. Atherosclerosis, for example, is arguably a condition caused by macrophage dysfunction, in which macrophages fail to clear excess cholesterol from blood vessel walls. Neurodegenerative conditions such as Alzheimer's disease, on the other hand, are characterized by the presence of activated, senescent, and overly inflammatory microglia. Can these cells be made more resilient to the aged tissue environment, made less inflammatory, made better at the task of waste clearance? Perhaps, as the work here indicates. Genetic and experimental evidence suggests that Alzheimer's disease (AD) risk alleles and genes may influence disease susceptibility by altering the transcriptional and cellular responses of macrophages, including microglia, to damage of lipid-rich tissues like the brain. Recently, single cell RNA sequencing studies identified similar transcriptional activation states in subpopulations of macrophages in aging and degenerating brains and in other diseased lipid-rich tissues. We collectively refer to these subpopulations of microglia and peripheral macrophages as disease-associated and lipid-associated cells, here DLAMs for b...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs