• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Feb 1991; 87(2): 591–596.
PMCID: PMC296347

Influence of age on the metabolism of plasma low density lipoproteins in healthy males.

Abstract

The plasma concentration of the atherogenic low density lipoproteins (LDL) increases with age. To clarify the mechanism of this change, we studied the kinetics of autologous 125I-LDL apolipoprotein B (apo B) in 41 normolipidemic, nonobese healthy males. For comparison, they were divided into three age groups: young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n = 12). The levels of plasma LDL cholesterol and LDL apo B increased from respectively 3.4 +/- 0.1 (SEM) mmol/liter and 86 +/- 2 mg/dl in the young to 4.1 +/- 0.1 mmol/liter and 95 +/- 3 mg/dl in the old (P less than 0.01), and this increase was linked to a progressively decreased (r = -0.38, P less than 0.02) fractional catabolic rate of LDL apo B (0.348 +/- 0.010 pools per day in the young vs. 0.296 +/- 0.009 pools per day in the old, P less than 0.01). The production rate of LDL apo B did not differ significantly between the groups. The reduced fractional catabolic rate of LDL apo B in the old was not associated with a decrease in binding affinity of the LDL particle to its receptor, as judged from its ability to compete for 125I-LDL fibroblast binding. When hepatic LDL receptor expression was stimulated by cholestyramine treatment in six old males, their LDL apo B fractional catabolic rate increased to the levels observed in the young subjects. We conclude that the increase in LDL which normally occurs with age is explained by a reduced capacity for its removal, and hypothesize that this is mediated via a reduced hepatic LDL receptor expression.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986 Nov 28;256(20):2835–2838. [PubMed]
  • Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987 Nov 12;317(20):1237–1245. [PubMed]
  • Heiss G, Tamir I, Davis CE, Tyroler HA, Rifkand BM, Schonfeld G, Jacobs D, Frantz ID., Jr Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation. 1980 Feb;61(2):302–315. [PubMed]
  • Abbott RD, Garrison RJ, Wilson PW, Epstein FH, Castelli WP, Feinleib M, LaRue C. Joint distribution of lipoprotein cholesterol classes. The Framingham study. Arteriosclerosis. 1983 May-Jun;3(3):260–272. [PubMed]
  • Miller NE. Why does plasma low density lipoprotein concentration in adults increase with age? Lancet. 1984 Feb 4;1(8371):263–267. [PubMed]
  • Havel RJ. The formation of LDL: mechanisms and regulation. J Lipid Res. 1984 Dec 15;25(13):1570–1576. [PubMed]
  • Vega GL, Grundy SM. Mechanisms of primary hypercholesterolemia in humans. Am Heart J. 1987 Feb;113(2 Pt 2):493–502. [PubMed]
  • Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. [PubMed]
  • Rudling MJ, Reihnér E, Einarsson K, Ewerth S, Angelin B. Low density lipoprotein receptor-binding activity in human tissues: quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo. Proc Natl Acad Sci U S A. 1990 May;87(9):3469–3473. [PMC free article] [PubMed]
  • Brown MS, Goldstein JL. Lipoprotein receptors in the liver. Control signals for plasma cholesterol traffic. J Clin Invest. 1983 Sep;72(3):743–747. [PMC free article] [PubMed]
  • Mahley RW, Innerarity TL. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. [PubMed]
  • Grundy SM, Vega GL, Bilheimer DW. Kinetic mechanisms determining variability in low density lipoprotein levels and rise with age. Arteriosclerosis. 1985 Nov-Dec;5(6):623–630. [PubMed]
  • Meddings JB, Dietschy JM. Regulation of plasma levels of low-density lipoprotein cholesterol: interpretation of data on low-density lipoprotein turnover in man. Circulation. 1986 Oct;74(4):805–814. [PubMed]
  • Einarsson K, Nilsell K, Leijd B, Angelin B. Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N Engl J Med. 1985 Aug 1;313(5):277–282. [PubMed]
  • Eriksson M, Berglund L, Rudling M, Henriksson P, Angelin B. Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma. J Clin Invest. 1989 Sep;84(3):802–810. [PMC free article] [PubMed]
  • Bilheimer DW, Eisenberg S, Levy RI. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. [PubMed]
  • Carlson K. Lipoprotein fractionation. J Clin Pathol Suppl (Assoc Clin Pathol) 1973;5:32–37. [PMC free article] [PubMed]
  • Lopes-Virella MF, Stone P, Ellis S, Colwell JA. Cholesterol determination in high-density lipoproteins separated by three different methods. Clin Chem. 1977 May;23(5):882–884. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • MATTHEWS CM. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. [PubMed]
  • Langer T, Strober W, Levy RI. The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J Clin Invest. 1972 Jun;51(6):1528–1536. [PMC free article] [PubMed]
  • Kesaniemi YA, Grundy SM. Significance of low density lipoprotein production in the regulations of plasma cholesterol level in man. J Clin Invest. 1982 Jul;70(1):13–22. [PMC free article] [PubMed]
  • Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed]
  • Witztum JL, Young SG, Elam RL, Carew TE, Fisher M. Cholestyramine-induced changes in low density lipoprotein composition and metabolism. I. Studies in the guinea pig. J Lipid Res. 1985 Jan;26(1):92–103. [PubMed]
  • Aviram M, Lund-Katz S, Phillips MC, Chait A. The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells. J Biol Chem. 1988 Nov 15;263(32):16842–16848. [PubMed]
  • Mahley RW, Hui DY, Innerarity TL, Weisgraber KH. Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. J Clin Invest. 1981 Nov;68(5):1197–1206. [PMC free article] [PubMed]
  • Lee HC, Paz MA, Gallop PM. Low density lipoprotein receptor binding in aging human diploid fibroblasts in culture. J Biol Chem. 1982 Aug 10;257(15):8912–8918. [PubMed]
  • Bilheimer DW, Ho YK, Brown MS, Anderson RG, Goldstein JL. Genetics of the low density lipoprotein receptor. Diminished receptor activity in lymphocytes from heterozygotes with familial hypercholesterolemia. J Clin Invest. 1978 Mar;61(3):678–696. [PMC free article] [PubMed]
  • Bierman EL, Albers JJ, Chait A. Effect of donor age on the binding and degradation of low density lipoproteins by cultured human arterial smooth muscle cells. J Gerontol. 1979 Jul;34(4):483–488. [PubMed]
  • Ahlberg J, Angelin B, Einarsson K. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and biliary lipid composition in man: relation to cholesterol gallstone disease and effects of cholic acid and chenodeoxycholic acid treatment. J Lipid Res. 1981 Mar;22(3):410–422. [PubMed]
  • Crouse JR, Grundy SM, Ahrens EH., Jr Cholesterol distribution in the bulk tissues of man: variation with age. J Clin Invest. 1972 May;51(5):1292–1296. [PMC free article] [PubMed]
  • Spady DK, Dietschy JM. Interaction of aging and dietary fat in the regulation of low density lipoprotein transport in the hamster. J Lipid Res. 1989 Apr;30(4):559–569. [PubMed]
  • Ballantyne CM, Vega GL, East C, Richards G, Grundy SM. Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis. Metabolism. 1987 Mar;36(3):270–276. [PubMed]
  • Tint GS, Ginsberg H, Salen G, Le NA, Shefer S. Chenodeoxycholic acid normalizes elevated lipoprotein secretion and catabolism in cerebrotendinous xanthomatosis. J Lipid Res. 1989 May;30(5):633–640. [PubMed]
  • Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest. 1981 May;67(5):1361–1369. [PMC free article] [PubMed]
  • Gordon DJ, Rifkind BM. Treating high blood cholesterol in the older patient. Am J Cardiol. 1989 May 2;63(16):48H–52H. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...