Interrelationships among HDL metabolism, aging, and atherosclerosis.
HDL plasma concentrations decline with age in prospective studies. Decline in HDL concentration and function may occur secondary because of hormonal changes, inflammatory processes, and diabetes mellitus. Beyond these effects specific aging processes may be involved. Replicative aging, the telomere-driven loss of divisional capacity, is a species-specific aging mechanism that may decrease HDL concentration and function. Cross-sectionally, by contrast, HDL levels do not change much or even slightly increase with age, suggesting that only people with still high HDL concentrations survive. A selection bias by HDL lowering genetic variation may explain why HDL deficiency is extremely rare among centenarians. Vice versa, HDL may modulate the aging process, not only by its well-known antiatherogenic effects, eg, its ability to remove cellular lipids and by antiatherogenic pleiotropic effects on cell survival, but possibly also by direct interfering with aging signaling or survival factor KLOTHO. Most of the current findings, however, are based on cell culture and selected animal experiments and await further confirmation by appropriate in vivo models.
Walter
Michael
M
Department of Laboratory Medicine and Pathobiochemistry, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. m.walter@charite.de
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D001692:Biological Transport; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D012307:Risk Factors
D008076:Cholesterol, HDL; D005966:Glucuronidase; D000090265:Klotho Proteins