CHANGES IN THE LEVELS OF ENZYMES WHICH MODULATE THE ANTIOXIDANT BALANCE OCCUR DURING AGING AND CORRELATE WITH CELLULAR-DAMAGE

Oxidative metabolism produces a flux of superoxide anions that must be removed from the cellular environment if the cell is to survive. The levels of antioxidant enzyme involved in the elimination of superoxide anions and/or hydrogen peroxide were investigated in an attempt to co rrelate any changes in the levels of these enzymes during aging with c hanges in free radical mediated cellular damage. Cu/Zn superoxide dism utase (Sod1), glutathione peroxidase (Gpx1) and catalase levels were m easured in a number of organs during murine aging. Sod1 enzyme activit y rose during aging in all organs studied, while the levels of both Gp x1 and catalase showed organ specific profiles. Both organs in which l ipid peroxidation damage (which was used as a marker of free radical m ediated damage) increased with age, namely the brain and small intesti ne, also showed a significant increase in the ratio of Sod1 to Gpx1 en zyme activity. In organs where either the ratio of Sod1/Gpx1 activity or Sod1/catalase levels (in the lung only) ratios were maintained duri ng aging, no increased lipid peroxidation damage was detected. In the lung where Sod1/Gpx1 ratio did increase, Sod1/catalase remained consta nt and this was able to provide protection during aging. Thus our data shows that alterations in the balance between first and second steps of the antioxidant pathway correlate with cellular damage, and that th is may contribute to the aging changes seen in some organs.