The reality of aging viewed from the arterial wall.pdfVIP

Artery Research (2013) 7, 73e80 Available online at journal homepage: /locate/artres The reality of aging viewed from the arterial wall* Edward G. Lakatta* Laboratory of Cardiovascular Science, 5600 Nathan Shock Drive, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA Any discussion about any aspect of aging cannot beg the issue of what aging is. This is a tough question, and there are numerous perspectives regarding the answer. My view is that aging is “a shift in an organism’s reality.” So what’s reality? This is another tough question. My view is that reality can be comprehensively de?ned as a system of mutual enslavement of DNA and its environment. If this appears to be a na¨?ve assessment of reality, check out what constitutes the DNA environment (Fig. 1). The white arrows in the ?gure indicate continual bidirectional signaling that must occur to sustain our existence. In this context, aging can be construed as a series of failures of the signaling within the DNA environmental system. A general description of some failing interactions in this system includes: generation of signals, sensing of signals, signal transmission, response to signals, and proteostasis. Viewing the reality of aging from the arterial wall begins with the realization that arterial diseases, e.g. atherosclerosis and hypertension, are rampant in Western society, and increase exponentially with advancing age. Progressive changes occur throughout life in the structure and function of central arteries in numerous species. These changes include diffuse intimal and medial thickening, and enhanced stiffening.1 Since the likelihood for predominantly systolic hypertension and atherosclerosis to occur increases in epidemic proportion among older persons1,2 (Fig. 2), it is reasonable to hypothesize that speci?c mechanisms that underlie alterations in the arterial substrate that accompany “aging” may be intimately linked to the age-associated exponential increase in