Aging Aging

Damage to Mitochondria 243synthesis, that is, with the main function of mitochondria. In our opinion, this justifiesfurther application of the above techniques to elucidate the specific role played bymitochondria in cellular aging under normal and experimentally altered conditions.8. Another proof of the usefulness of flow cytometry study of mitochondrial agingis provided by our finding of an increased DhRh oxidation in mitochondria isolatedfrom the liver of old rats as compared to those isolated from young animals,which suggests that senescence is accompanied by an increased oxygen stress.References1. Harman, D. (1956) Aging: a theory based on free radical and radiation chemistry.J. Gerontol. 11, 298–300.2. Miquel, J. and Fleming, J. (1986) Theoretical and experimental support for an “oxygenradical-mitochondrial injury hypothesis of cell aging, in Free Radicals, Agingand Degenerative Diseases (Johnson, J. E., Jr., Walford, R., Harman, D., and Miquel,J., eds.) Alan R. Liss, New York, pp. 51–74.3. Miquel, J. (l998) An update on the oxygen stress-mitochondrial mutation theory ofaging: genetic and evolutionary implications. Exp. Gerontol. 33, 113–126.4. Yen, T. C., Chen, Y. S., King, K. L., Yeh, S. H., and Wei, Y. H. (1989) Liver mitochondrialrespiratory functions decline with age. Biochem. Biophys. Res. Commun.165, 994–1003.5. García de la Asunción, J., Millán, A., Pla, R., Bruseghini, L., Esteras, A., Pallardo,F. V., Sastre, J., and Viña, J. (1996) Aging of the liver: age associated oxidativedamage to mitochondrial DNA. FASEB J. 10, 333–338.6. Sastre, J., Pallardo, F. V., Pla, R., Pellin, A., Juan, G., O’Connor, E., Estrela, J. M.,Miquel, J., and Viña, J. (1996) Aging of the liver: age associated mitochondrialdamage in intact hepatocytes. Hepatology 24, 1199–1205.7. Sastre, J., Millan, A., García de la Asunción, J., Pla, R., Juan, G., Pallardó, F. V.,O’Connor, E., Martin, J. A., Droix-Lefaix, M. T., and Viña, J. (1998) A Ginkgobiloba extract (Egb 761) prevents mitochondrial aging by protecting against oxidativestress. Free Radic. Biol. Med. 24, 298–304.8. Hagen, T. M., Yowe, D. L., Bartholomew, J. C., Wehr, C. M., Do, K. L., Park, J.-Y.,and Ames, B. N. (1997) Mitochondrial decay in hepatocytes from old rats: membranepotential declines, heterogeneity and oxidants increase. Proc. Natl. Acad.Sci. USA 94, 3064–3069.9. Chen, L. B. (1989) Mitochondrial membrane potential in living cells. Ann. Rev.Cell Biol. 4, 155–181.10. Darley-Usmar, V. M., Rickwood, D., and Wilson, M. T., eds. (1987) Mitochondria:a Practical Approach, IRL, Oxford, pp. 1–16.11. Ferrandiz, M. L., Martínez, M., De Juan, E., Díez, A., Bustos, G. and Miquel, J.(1994) Impairment of mitochondrial oxidative phosphorylation in the brain of agedmice. Brain Res. 644, 335–338.12. Martínez, M., Ferrándiz, M. L., Díez, A., and Miquel, J. (1995) Depletion of cytosolicGSH decreases the ATP levels and viability of synaptosomes from aged mice butnot from young mice. Mech. Ageing Dev. 84, 77–81.