The Role of Capillaries in the Lesser Ailments of Old Age and in Alzheimer’s Disease and Vascular Dementia: The Potential of Pro-Therapeutic Angiogenesis

Abstract

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and people, including those with Alzheimer's disease. The deficiency of AG factors is analogous to that of certain hormones (e.g., testosterone) whose blood levels also decline with age. In theory, therapeutic angiogenesis employing recombinant AG factors is a tenable treatment for the lesser ailments of old age and may improve the later years of human life. An optimal administration route may be intranasal.

Capillaries, Old Age and Alzheimer’s Disease

“…The former involve arthritis, diabetes, atrial fibrillation, Parkinson's disease, or other distressing illnesses and are not a concern here. The latter, the lesser ailments, include minor symptoms, such as general muscle weakness, cold intolerance, memory lapses for names or words, and momentarily dozing, especially during the evening hours [6]. Also included are physical signs, such as wrinkled skin on the face and dorsum of the hands and the slow healing of bruises and abrasions.…”

“…Capillaries are formed and maintained by angiogenic growth factors (AGFs), whose levels are genetically programmed during early development and throughout life. A decline in AGFs in the aged has been described in seven other reports and noted in five organ systems --i.e., the brain, muscles, kidney, mononuclear cells, and vein wall [5,6]. Among the AGFs are vascular endothelial growth factor (VEGF), fibroblast growth factors (FGFs), and other such factors.…”

“…As discussed elsewhere, a reduced CD in aged persons and animals has been described in over 40 reports and noted in many organ systems --i.e., brain, muscle, skin, larynx, lung, colon, kidney and vasa vasorum [5,6]. Capillaries are formed and maintained by angiogenic growth factors (AGFs), whose levels are genetically programmed during early development and throughout life.…”

“…They have provided 80 data pairs showing age-linked reduced CD and declining AG. These paired figures have been presented elsewhere in tables and are the basis for a hypothesis that the reduced capillary numbers in the elderly account in part for their lesser ailments [4][5][6].…”

“…Whether these changes progress to reduced capillary numbers by cellular atrophy has not been demonstrated and is not considered further here. However, the widespread reduced capillary density (CD) found in aged animals and people has been correlated with diminished levels of angiogenic growth factors (AGFs) [4][5][6].…”