Prevention of lipofuscin development in neurons by anti-oxidants.

It was documented that ageing is associated with a progressive and highly significant proliferation of the total number of light microscopically visible lipofuscin granules in the grey substance of sections of the cervical spinal cord of Balb/c mice. The mean total numbers (+/- standard errors) of lipofuscin granules in standard sections of the glutaraldehyde-osmium fixed, epon embedded spinal cords that were examined with a phase contrast light microscope in 1 week, 1 month, 8 months and 18 months old mice were 0, 269 +/- 56, 1101 +/- 82 and 2464 +/- 318, respectively. The population densities of multiglobular lipofuscin units as seen with the electron microscope in random spinal cord neurons of the same 4 age groups corresponded well with the above quantitative, light microscopic data. Continuous treatment for 8 months with either the natural anti-oxidant Vitamin E (alpha-tocopherol) at 40 mg/mouse/week or the synthetic anti-oxidant butylated hydroxytoluene at about 100 mg/mouse/week diminished significantly the proliferation of lipofuscin granules in spinal cord neurons that developed during that period of ageing. No toxicity of any sort was caused by these two treatments. These results provide support for the peroxide theory of lipofuscin biogenesis and encourage further exploration of the possibilities of obtaining greater anti-lipofuscin effects with less molecular bulk of antioxidants.