Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Sep;75(9):4431–4435. doi: 10.1073/pnas.75.9.4431

Age-dependent relaxation of gene repression: Increase of endogenous murine leukemia virus-related and globin-related RNA in brain and liver of mice

Tetsuya Ono 1, Richard G Cutler 1
PMCID: PMC336129  PMID: 212751

Abstract

A progressive loss in the ability of cells to maintain their normal specialized states of differentiation could be the common denominator underlying much of the physiology and pathology associated with the mammalian aging process. We investigated this possibility by searching for an age-dependent derepression of endogenous genes in tissues in which they are not normally expected to be expressed. Complementary DNA (cDNA) probes to globin genes and to the murine leukemia type C RNA virus (MuLV) genome were used to detect the presence of RNA complementary to these genes in RNA extracted from brain and liver in young and old mice. Significant amounts of globin RNA were found in brain nuclei and cytoplasm. No age difference was found in the globin RNA sequences present, but the number of globin RNA molecules increased from about 15 in 6-month to 34 in 27-month-old animals for nuclei and 280 in 6-month to 500 in 27-month-old animals for cytoplasm. Similar results were found for liver. RNA complementary to the MuLV cDNA probe was also found but, in contrast to globin, the different RNA sequences increased in both brain and liver nuclei from about 45% of the MuLV genome in 6-month to 72% in 27-month-old animals. The number of MuLV-related RNA molecules remained constant at about 22 and 38 per nuclei for brain and liver, respectively. Derepression of genes of this magnitude could result in a time-dependent increase in virus-related diseases and a general deterioration of the organism.

Keywords: gene regulation, dedifferentiation, primary aging process, cDNA-RNA hybridization

Full text

PDF
4431

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axel R., Feigelson P., Schutz G. Analysis of the complexity and diversity of mRNA from chicken liver and oviduct. Cell. 1976 Feb;7(2):247–254. doi: 10.1016/0092-8674(76)90024-6. [DOI] [PubMed] [Google Scholar]
  2. Chattopadhyay S. K., Lowy D. R., Teich N. M., Levine A. S., Rowe W. P. Qualitative and quantitative studies of AKR-type murine leukemia virus sequences in mouse DNA. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):1085–1101. doi: 10.1101/sqb.1974.039.01.124. [DOI] [PubMed] [Google Scholar]
  3. Cutler R. G. Evolution of human longevity and the genetic complexity governing aging rate. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4664–4668. doi: 10.1073/pnas.72.11.4664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cutler R. G. Transcription of unique and reiterated DNA sequences in mouse liver and brain tissues as a function of age. Exp Gerontol. 1975 Feb;10(1):37–59. doi: 10.1016/0531-5565(75)90014-5. [DOI] [PubMed] [Google Scholar]
  5. Elder J. H., Jensen F. C., Bryant M. L., Lerner R. A. Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family. Nature. 1977 May 5;267(5606):23–28. doi: 10.1038/267023a0. [DOI] [PubMed] [Google Scholar]
  6. Field E. J. Scrapie: a review of its relation to human disease and ageing. J Med Genet. 1976 Dec;13(6):479–495. doi: 10.1136/jmg.13.6.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Finch C. E. Enzyme activities, gene function and ageing in mammals. (Review). Exp Gerontol. 1972 Feb;7(1):53–67. doi: 10.1016/0531-5565(72)90035-6. [DOI] [PubMed] [Google Scholar]
  8. Friend C., Preisler H. D., Scher W. Studies on the control of differentiation of murine virus-induced erythroleukemic cells. Curr Top Dev Biol. 1974;8:81–101. doi: 10.1016/s0070-2153(08)60606-7. [DOI] [PubMed] [Google Scholar]
  9. Getz M. J., Birnie G. D., Paul J. Transcription of in vitro polyadenylated ribonucleic acid with reverse transcriptase. Biochemistry. 1974 May 7;13(10):2235–2240. doi: 10.1021/bi00707a033. [DOI] [PubMed] [Google Scholar]
  10. Getz M. J., Elder P. K., Benz E. W., Jr, Stephens R. E., Moses H. L. Effect of cell proliferation on levels and diversity of poly(A)-containing mRNA. Cell. 1976 Feb;7(2):255–65. doi: 10.1016/0092-8674(76)90025-8. [DOI] [PubMed] [Google Scholar]
  11. Getz M. J., Reiman H. M., Jr, Siegal G. P., Quinlan T. J., Proper J., Elder P. K., Moses H. L. Gene expression in chemically transformed mouse embryo cells: selective enhancement of the expression of C type RNA tumor virus genes. Cell. 1977 Aug;11(4):909–921. doi: 10.1016/0092-8674(77)90302-6. [DOI] [PubMed] [Google Scholar]
  12. Groudine M., Weintraub H. Rous sarcoma virus activates embryonic globin genes in chicken fibroblasts. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4464–4468. doi: 10.1073/pnas.72.11.4464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huebner R. J. The endogenous origin and transmission of RNA viral genomes that code for cancer. Recent Results Cancer Res. 1976;(54):63–91. doi: 10.1007/978-3-642-80997-2_6. [DOI] [PubMed] [Google Scholar]
  14. Humphries S., Windass J., Williamson R. Mouse globin gene expression in erythroid and non-erythroid tissues. Cell. 1976 Feb;7(2):267–277. doi: 10.1016/0092-8674(76)90026-x. [DOI] [PubMed] [Google Scholar]
  15. Kleene K. C., Humphreys T. Similarity of hnRNA sequences in blastula and pluteus stage sea urchin embryos. Cell. 1977 Sep;12(1):143–155. doi: 10.1016/0092-8674(77)90192-1. [DOI] [PubMed] [Google Scholar]
  16. Leuenberger H. G., Kunstýr I. Gerontological data of C57BL/6J mice. II. Changes in blood cell counts in the course of natural aging. J Gerontol. 1976 Nov;31(6):648–653. doi: 10.1093/geronj/31.6.648. [DOI] [PubMed] [Google Scholar]
  17. Perlman S. M., Ford P. J., Rosbash M. M. Prescence of tadpole and adult globin RNA sequences in oocytes of Xenopus laevis. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3835–3839. doi: 10.1073/pnas.74.9.3835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Walford R. L. Immunologic theory of aging: current status. Fed Proc. 1974 Sep;33(9):2020–2027. [PubMed] [Google Scholar]
  19. Young B. D., Paul J. Absence from the mouse genome of DNA sequences related to the globin gene family. J Mol Biol. 1975 Aug 25;96(4):783–789. doi: 10.1016/0022-2836(75)90153-9. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES