There are many theories of aging, some with a broader scope, focused on the high level or the evolutionary explanation for aging and all of its variations in pace, and others that are more limited, examining just a few aspects of age-related decline and in search of the principle mechanisms that cause that decline. Today's example is one of the more compact theories of aging, restricting itself to considering the creation and maintenance of the network of capillaries that supplies tissues. The oxygen and nutrients carried by blood cannot perfuse far beyond blood vessels, and so every last cubic millimeter of the body must be reached by the circulatory system, where it branches out into the smallest and most numerous blood vessels, those too small to be discerned by the naked eye.

What does it tell us about aging that capillary density appears to decrease in older mammals? Cardiovascular disease is of course well known to be a major cause of mortality, but much of the focus there is on the stiffening of major blood vessels, hypertension, and dysfunction and remodeling of heart tissue. These are larger-scale phenomenon, undeniably important, but does their importance overwhelm what is going on at the small scale, in the network of capillaries throughout the body? The researchers here argue that the small scale is just as important.

One item to bear in mind when reading the paper here is that mitochondrial dysfunction of a fairly general sort, a global loss of function, is implicated in many aspects of aging. Mitochondria are the power plants of the cell, using nutrients to generate chemical energy store molecules. One might ponder on a connection between reduced capillary coverage and reduced mitochondrial activity due to a lack of nutrients; certainly a great deal of neurodegenerative disease research focuses on vascular dysfunction and consequently reduced delivery of oxygen and nutrients to the brain.

The other principle point made by the authors of this paper is that there may be a short path to therapies that can partially compensate for the loss of capillary density by spurring angiogenesis, the creation of new blood vessels. Angiogenesis has been fairly well studied in the cancer research community and elsewhere, and there are a wide range of targets and drug candidates to either increase or decrease angiogenesis rates. Since testing effectiveness would be a comparatively rapid process, it might be worth trying this approach even though it doesn't address the underlying reasons for the loss of capillary density. As to what those reasons might be, we can speculate; perhaps loss of stem cell activity, perhaps changes in the extracellular matrix, or perhaps chronic inflammation that disrupts the normal processes of regeneration and angiogenesis, to pick a few options for further discussion.

Pro-Angiogenesis Therapy and Aging: A Mini-Review