Lipoprotein modification and atherosclerosis in aging

The development of extensive atherosclerosis of major arteries of the heart, brain, and lower extremities is a particularly frequent problem in elderly individuals and is responsible for the majority of the cardiovascular morbidity and mortality in this population. Although the frequency and severity of this problem is well recognized, there has been relatively little investigation of the effects of aging on the development of atherosclerosis. Work by a number of investigators over the last 10-15 years has demonstrated that modifications of lipoproteins, resulting from oxidative stress, glycoxidation, formation of AGE, or other processes may play an important role in atherosclerosis. As described in this review, the aging process may enhance lipoprotein modification and atherosclerosis in several ways. Conditions such as hypertension, diabetes, and menopause all increase in frequency with advancing age and may contribute both directly and indirectly to lipoprotein modification and vascular injury. Additionally, in some studies of older animals and humans, there seems to be evidence for greater in vivo oxidative stress. Whether this is a specific consequence of aging and associated medical conditions, or related to differences in dietary fatty acid or antioxidant content or other lifestyle differences is currently unknown. One important consequence of this may be enhanced susceptibility of lipoproteins to oxidation. Additional study of lipoprotein modifications associated with aging is clearly needed, and may provide new insight and solutions to the common problem of atherosclerosis in the elderly.