Microglia Phagocytosis Contributes to Neural Stem Cell Loss in the Aging Subventricular Zone

Aging, defined as the increasing probability of mortality over time due to organismal declines in function, is the leading risk factor for cognitive decline and associated dementias. In adults 45 years of age and older in the United States (U.S.), subjective cognitive decline is prevalent in 1/9 of these adults and increases to 1/7.6 in Texas. The effects of cognitive decline can be felt in most aspects of everyday life. 1/3 of individuals who reported subjective cognitive decline also report abnormal levels of stress, emotional problems, and depression. Furthermore, 1/2 of individuals who reported subjective cognitive decline also reported having to give up day-to-day activities such as cooking, cleaning, social engagements, and driving. These declines in function generally lead to the inability to care for oneself and having to be taken care of either by family or in a senior living center. This raises a problem as the aging population is increasingly growing in size and cost. From 2015-2050, the World Health Organization (WHO) predicts that the population of people over the age of 60 will increase from 12 to 22% out of the total population. In the U.S., this increase is predicted to raise the amount of money spent on healthcare from 20% to 28% of the share of the gross domestic product. It should be noted that this increase is not linear, meaning the world’s population is aging much quicker than ever in recorded history. In fact in 2020, the same year I am writing this thesis, number of people over the age of 60 has now surpassed the number of children 5 years or younger. Thus, investigating the cellular mechanisms of cognitive decline are essential to address this growing problem and build a knowledge base for subsequent development of therapies designed for cognitive rejuvenation. However, with the role of adult neural stem cells (NSCs) being crucial in a multitude of homeostatic brain functioning that keep it youthful and resilient, little is known about how and why adult NSCs age.