Research Angiogenesis and Wound Healing, Impaired Angiogenesis in the Elderly

Experimental Evidence

As aging occurs, the angiogenic process deteriorates. Experimental evidence has shown that the ability to generate new blood vessels decreases in older animals.⁹⁷ This has been shown to correlate, among other factors, with the decline of the functioning of macrophages.⁹⁸ Macrophages produce VEGF, vascular endothelial growth factor, which is a vital part of the wound healing process. When macrophage function is negatively affected, VEGF production declines, and wound healing is directly impacted.⁹⁹ Additionally, advancing age has been shown to affect capillary density, specifically in wound specimens in multiple-aged experimental models.¹⁰⁰ Diminishment of capillary density also contributes to decline in angiogenesis, thus impeding wound healing.

Clinical Evidence

As far back as 1968, a study demonstrated that post-surgical dehiscence is increased in elderly patients. More recently, it was shown that elderly patients are characterized by delayed epithelialization in the wound healing process when compared to younger patients with comparable wounds.¹⁰¹

Another study investigated differences in sunburn reactions quantitatively in varying age groups. Results showed that the skin of the older group (62-86 years of age) was characterized by impaired mast cell and endothelial cell response compared to the skin of the younger group (22-26 years of age).¹⁰² Mast cells and endothelial cells are, like macrophages, critical in the wound healing process. Mast cells are key in mounting an inflammatory response to infections. If they are impaired, the wound (or burn) heals significantly more slowly. Endothelial cells form the basis or structure of normal skin; if their function is impaired, the skin will take much longer to regain its healthy condition.

Additionally, growth factors other than VEGF are important in the wound healing process and one of them in particular, insulin-like growth factor (ILGF) has been investigated as being especially critical.¹⁰³ ILGF is released by platelets and may determine, in turn, the release of other growth factors including VEGF. Thus, if the presence of ILGF is diminished, so too will be the presence of VEGF and this will directly contribute to impaired wound healing.

In spite of the fact that the elderly generally are characterized by decreased angiogenic response, it is nevertheless important to differentiate angiogenic mechanisms between, for example, an elderly patient with a diabetic foot ulcer and one with a pressure ulcer. That is, the clinician should not assume that because the patient is elderly, he should not be expected to heal within a reasonable timeframe or not at all, regardless of type of wound. Once the diagnosis has been specified as to not only type of wound, but stage of the wound, the appropriate team of clinicians can provide therapy targeted to the wound. This differentiation is vital in the treatment of elderly patients suffering from chronic wounds.¹⁰⁴