Abstract
It appears that consistent changes in the levels of activity of a small cohort of genes(probably less than 1% of all active genes)occur in all mammalian cells during ageing. We have studied this phenomenon in rat liver using an optimised form of differential display. During this investigation we observed one gene which exhibited a decline in expression in livers from young adult (6 months) to aged adult (24 months) animals. The differential expression of this gene was confirmed by single strand conformational polymorphism (SSCP) gel analysis and Northern blotting. Densitometry of the latter indicated that there was adecline of 35% in its expression with age. Characterisation of the isolated PCR fragment demonstrated it to code for the alpha subchain of the complement 4 binding protein (C4BP). The C4BP is a key regulatory protein of the complement system and this observation therefore indicates that a decline in the efficiency of the complement system may be an important factor in the overall decline in immune function that has been observed during ageing.
Similar content being viewed by others
References
Ausubel FM, Brent R, Kingston RE, Moore DD, Seidmann JG, Smith JA and Struhl K (eds) (1993) Current Protocls in Molecular Biology. Greene Publishing Associates and John Wiley and Sons, New York
Barnum SR (1991) C4b-binding protein, a regulatory protein of complement. Immunol Res 10: 28-42
Barnum SR and Dahlback B (1990) C4b-binding protein, a regulatory component of the classical pathway of complement, is an acute-phase protein and is elevated in systemic lupus erythematosis. Complement Inflamm 7: 71-77
Bilder GE (1975) Studies on immune competence in rat: changes with age, sex and strain. J Gerontol 30: 641-646
Carter D, Goepel JR, Winship PR and Goyns MH (1999) Identification of different patterns of gene expression in low and high grade non-Hodgkin's lymphomas by differential display. Leuk Lymp 33: 343-350
Charlton MA, Merry BJ and Goyns MH (1999). Differential display analysis can reveal patterns of gene expression in immortalised hepatoma cells which are similar to those observed in young adult but not old adult liver cells. Cancer Lett 143: 45-50
Dahlback B (1983) Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. Biochem J 209: 847-856
Garcia OC, Sanchez-Corral P and Rodriuez de Cordoba S (1995) Isoforms of human C4b-binding protein. Differential modulation on the C4BPA and C4BPB genes by acute phase cytokines. J Immunol 155: 4037-4043
Garcia de Frutos P, Hardig Y and Dahlback B (1995) Serum amyloid P component binding to C4b-binding protein. J Biol Chem 270: 26950-26955
Gardner ID and Remington JS (1988) Age-related decline in the resistance to infection with intracellular pathogens. Infection Immunity 16: 593-598
Goyns MH, Charlton MA, Dunford JE, Lavery WL, Merry BJ, Salehi M and Simoes DCM (1998) Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes. Mech Age Develop 101: 73-90
Grierson AJ, Hodgknis MA, Hancock BW, Goepel JR, Royds J and Goyns MH (1996) Investigation of the RB-1 tumour supressor gene in a United Kingdom series of non-Hodgkins lymphomas. Leuk Lymph 23: 353-363
Hessing M, Van't Veer C and Bouma BN (1990) The binding site of human C4b-binding protein on complement C4 is located in the α-chain. J Immunol 144: 2632-2637
Hirokawa K, Utsuyama M, Katsura Y and Sado T (1988) Influence of age on the proliferation and peripheralisation of thymic T cells. Arch Pathol Lab Med 112: 13-21
Lee CK, Klopp RG, Weindruch R and Prolla TA (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285: 1390-1393
Lee CK, Weindruch R and Prolla TA (2000). Gene expression profile of the ageing brain in mice. Nature Genet 25: 294-297
Linskens MH, Feng J, Andrews WH, Enlow BE, Saati SM, Tonkin LA, Funk WD and Villeponteau B (1995) Cataloging altered gene expression in young and senescent cells using enhanced differential display. Nucleic Acid Res 23: 3244-3251
Ly DH, Lockhart DJ, Lerner RA and Schultz PG (2000) Mitotic misregulation and human aging. Science 287: 2486-2492
Makinodan T and Peterson WJ (1962) Relative antibody-formating capacity of spleen cells as a function of age. Proc Natl Acad Sci USA 48: 234-238
Merry BJ and Holehan AM (1994) Effects of diet on ageing In: Timiras PS (ed) Physiological Basis of Ageing, pp 285-310. CRC Press, Boca Raton, Florida
Pearson WR and Lipmann DJ (1988) Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85: 2444-2448
Pepys MB, Booth DR, Hutchinson WL, Gallimore JR, Collins PM and Hohenester E (1997) Amyloid P component. A critical review. Int J Expl Clin Invest 4: 274-295
Peterson WJ and Makinodan T (1972) Autoimmunity in aged mice. Occurrence of autoagglutinating factors in the blood of aged mice with medium to long life-span. Clin Expl Immunol 12: 273-290
Pisciotta AV, Westring DW, Deprey C and Walsh B (1967) Mitogenic effect of phytohaemagglutinin at different ages. Nature 215: 193-194
Radl J and Hollander CFJ (1973) Homogeneous immunoglobulins in sera of mice during ageing. Immunol 112: 2271-2273
Salehi M, Barron M, Merry BJ and Goyns MH (1999) Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing brain. Mech Age Develop 107: 61-71
Salehi M, Hodgkins MA, Merry BJ and Goyns MH (1996) Agerelated changes in gene expression revealed in the rat brain by differential display. Experientia 52: 888-891
Saeki T, Hirose S and Nukatsuka M (1989) Evidence that C4bbinding protein is an acute phase protein. Biochem Biophys Res Commun 164: 1446-1451
Scharfstein J, Ferreira A and Gigli I (1978) Human C4-binding protein. Isolation and characterisation. J Exp Med 148: 207-222
Sheerin A, Thompson K and Goyns MH (2001) Altered composition and DNA binding activity of the AP-1 transcription factor during the ageing of fibroblasts. Mech Age Develop 122: 1813-1824
Shelton DN, Chang E, Whittier PS, Choi D and Funk WD (1999) Microarray analysis of replicative senescence. Curr Biol 9: 939-945
Slagboom PE, de Leeuw WJ and Vijg J (1990) Messenger RNA levels and methylation patterns of GAPDH and beta-actin genes in rat liver, spleen and brain in relation to aging. Mech Age Develop 53: 243-257
Van Remmen H, Ward WF, Sabia RV and Richardson A (1995) Effect of age on gene expression and protein degradation In: Masoro EJ (ed) Handbook of Aging, pp 171-234. Oxford University Press, New York
Villiers MB, Reboul A and Thielens NM (1981) Purification and characterisation of C4-binding protein from human serum. FEBS Lett 132: 49-53
Welsh TR, Forristal J and Bouma L (1986) Relationship between the component and regulatory proteins of the classical pathway C3 convertase. J Lab Clin Med 107: 529-533
Zaccardi RJ, Dahlback B and Muller-Eberhard HJ (1984) Characterization of the interaction between human C4b-binding protein with physiological ligands. J Biol Chem 259: 13674-13679
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lavery, L.W., Goyns, M.H. Decline in the expression of C4 binding protein alpha-chain gene during ageing of the rat liver. Biogerontology 3, 207–211 (2002). https://doi.org/10.1023/A:1016251929165
Issue Date:
DOI: https://doi.org/10.1023/A:1016251929165