On the role of cross-linking of cellular proteins in aging

Mech Ageing Dev. 1980 Sep-Oct;14(1-2):245-51. doi: 10.1016/0047-6374(80)90124-4.


Water-insoluble protein fractions increase in the brain cortical tissue and liver of rats during aging in both sexes. This suggests a possible increase in the cross-linking of proteins which may be due to the formation of, for example, hydroxyl free radicals during several metabolic processes. In vivo application of centrophenoxine causes a reversal of this phenomenon in old rats. In vitro experiments show that the generation of hydroxyl free radicals by chemical systems like homolysis of H2O2 by redox coupling with Fe2+ leads to Fe3+ conversion, results in the cross-linking of bovine serum albumin and the mixed proteins of liver or brain homogenates of young rats. The cross-linked proteins have a very much increased molecular weight, they become mostly insoluble even in 6 M urea. Dimethylaminoethanol, the effective part of the centrophenoxine molecules, is able to diminish the extent of cross-linking, acting most probably as a free-radical scavenger. The results are discussed in terms of the "membrane hypothesis of aging". A molecular basis is proposed for the anti-aging effect of centrophenoxine.

MeSH terms

  • Aging* / drug effects
  • Animals
  • Brain / metabolism*
  • Deanol / pharmacology
  • Ferrous Compounds / metabolism
  • Free Radicals
  • Liver / metabolism*
  • Macromolecular Substances
  • Oxidation-Reduction
  • Proteins / metabolism*
  • Rats
  • Serum Albumin, Bovine / metabolism
  • Solubility


  • Ferrous Compounds
  • Free Radicals
  • Macromolecular Substances
  • Proteins
  • Serum Albumin, Bovine
  • Deanol