White matter aging and its impact on brain function

 You competent? doctor has known of myelin problems from your stroke a long time ago, was anything done to solve it? NO? So, pure incompetence in action!

(My doctor told me I had a bunch of white matter hyperintensities but never showed me them on any scan, so I don't know the size, location or any intervention needed, because my doctor knew nothing and did nothing.)

demyelinating (23 posts to May 2012)

demyelination (7 posts to November 2021)

White matter aging and its impact on brain function

Janos Groh^1,2,3 janos.groh@tum.de ∙ Mikael Simons^1,2,3,4 mikael.simons@dzne.de

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Summary

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders. Understanding these changes is crucial for devising effective disease prevention strategies. Here, we will discuss the structural alterations in white matter that occur with aging and examine the cellular and molecular mechanisms driving these aging-related transformations. We highlight how the progressive disruption of white matter may initiate a self-perpetuating cycle of inflammation and neural damage.

Keywords

1. aging
2. white matter
3. myelin
4. neuroinflammation

Introduction

In his pioneering work, De Humani Corporis Fabrica (1543), Renaissance anatomist Andreas Vesalius provided one of the earliest descriptions of white matter structure, noting the corpus callosum as a whitish substance distinct from the softer, yellowish cerebrum.¹ Although Vesalius recognized that the corpus callosum connected the two hemispheres, he did not understand that its fibers originated from nerve cell bodies. At the time, white matter was believed to be composed of excretory ducts filled with a “spongy substance” and was thought to be the center of spirit and imagination.¹ Now, we know that white matter primarily consists of myelinated axons, glial cells, blood vessels, and extracellular matrix. Oligodendrocytes, the main cells in white matter, produce myelin sheaths that are crucial for fast signal transmission and for maintaining the functional and structural integrity of axons.^2,3 Because white matter largely lacks neuronal cell bodies and mainly serves to connect different gray matter areas, it has not received as much as attention as the cortical areas of the brain. Yet, its significance becomes evident when looking at its evolution in primates. Unlike neocortical gray matter, which grows in direct proportion to brain size, white matter mass has increased at a much higher rate, highlighting the crucial role of enhanced connectivity for higher brain function.⁴ Consequently, the proportion of white matter in the human brain has risen to about 40%, with myelinated axons being a major component.⁴ However, this expansion of white matter also introduces risks, providing a surface for diseases and the effects of aging. As we age, our white matter undergoes several changes. It experiences a reduction in overall volume and exhibits a decline in its microstructural integrity, and there is an accumulation of focal lesions, contributing to a decline in cognitive functions and to the risk for age-related neurological diseases, including dementia and stroke.^5,6,7,8 Many of these changes follow non-linear kinetics, starting slowly and then accelerating at a certain age.⁹ In this context, we explore the structural changes in white matter associated with aging and investigate the cellular and molecular mechanisms underlying these age-related transformations. We hypothesize that chronic inflammation and vascular changes are closely linked to the degeneration of myelin and axons with age.