Abstract
The exquisite sensitivity of mitochondrial transcription to oxidant stress suggests that chronic, low level oxidative stress may impair mitochondrial gene expression during the aging process. In this study, we assessed the effects of age and of life-prolonging, anti-oxidative dietary restriction (DR) regimens on sensitivity of mitochondrial transcription to oxidant stress. Studies were carried out using liver mitochondria isolated from male Fischer 344 rats of different ages (6, 12, 18, or 24 months) fed ad libitum (AL) or maintained on DR. Transcriptional capacity was assessed in isolated mitochondria challenged with different doses of either hydrophilic or hydrophobic peroxyl radicals generated by AAPH [2,2′-azobis-(2-amidino-propane) hydrochloride] or AMVN [2, 2′-azobis-(2,4,-dimethyl-valeronitrile), respectively].
The most striking effect was that DR increased resistance to AMVN nearly 400% at 6 months and nearly 700% at 24 months, relative to resistance in AL rats. Results also suggest that resistance to both AAPH and AMVN was decreased slightly in older AL rats, but was maintained in the DR rats. These results show that DR augments the defense systems that protect one of the mitochondria’s most vulnerable systems. This augmentation is one of the largest magnitude effects of DR yet observed against oxidative challenge.
Similar content being viewed by others
References
Kristal, B. S., B. P. Yu (1994) Aging and its modulation by caloric restriction. In: Yu, B. P., ed. Modulation of aging processes by dietary restriction. CRC Press, Boca Raton, pp. 1–35.
Shimokawa, I., Y. Higami (1994) Effect of dietary restriction on pathological processes. In: Yu, B. P., ed. Modulation of aging processes by dietary restriction. CRC Press, Boca Raton, pp. 247–266.
Yu, B. P. (1996) Aging, oxidative stress: Modulation by dietary restriction, Free Radical Biology & Medicine, 21, 651–668.
Yu, B. P. (1995) Modulation of oxidative stress as a means of life-prolonging action of dietary restriction. In: Cutler, R. G.; Packer, L.; Bertram, J.; Mori, A. (Eds.). Oxidative stress, Birkhäuser Verlag, Bassel, pp. 331–342.
Yu, B. P., R. Yang (1996) Critical evaluation of free radical theory of aging: a proposal of oxidative stress hypothesis, Annals of the New York Academy of Sciences, 786, 1–11.
Harman, D. (1956) Aging: a theory based on free radical and radiation chemistry, The Journals of Gerontology, 11, 289–300.
Kristal, B. S., B. P. Yu (1992) An emerging hypothesis: Synergistic induction of aging by free radicals and Maillard reactions, The Journals of Gerontology, 47, B107–B114.
Monnier, V. M. (1989) Toward a Maillard reaction theory of aging. In: Baynes, J. W.; Monnier, V. M., eds. The Maillard reaction in aging, diabetes and nutrition. Progress in Clinical and Biological Research, Alan R. Liss, New York, pp. 1–22.
Sohal, R. S., H. H. Ku, S. Agarwal, M. J. Forster, H. Lal (1994) Oxidative damage, mitochondrial oxidant generation and antioxidant defense during aging and in response to food restriction in the mouse, Mechanisms of Ageing and Development, 74, 121–133.
Weindruch, R. H., M. K. Cheung, M. A. Verity, R. L. Walford (1980) Modification of mitochondrial respiration by aging and dietary restriction, Mechanisms of Ageing and Development, 12, 375–395.
Laganiere, S., B. P. Yu (1987) Anti-lipoperoxidation action of food restriction, Biochemical and Biophysical Research Communication, 145, 1185–1191.
Chen, J. J., B. P. Yu (1996) Detoxification of reactive aldehydes in mitochondria: Effect of age and dietary restriction, Aging, Clinical and Experimental Research, 8, 334–340.
Yu, B. P., E. A. Suescun, S. Y. Yang (1992) Effect of age-related lipid peroxidation on membrane fluidity and phospholipase A2: Modulation by dietary restriction, Mechanisms of Ageing and Development, 65, 17–33.
Chung, M. H., H. Kasai, S. Nishimura, B. P. Yu (1992) Protection of DNA damage by dietary restriction, Free Radical Biology & Medicine, 12, 523–525.
Yu, B. P., J. J. Chen, C. M. Kang, M. Choe, Y. S. Maeng, B. S. Kristal (1996) Mitochondrial aging and lipoperoxidative products, Annals of the New York Academy of Sciences, 786, 44–56.
Kristal, B. S., J. J. Chen, B. P. Yu (1994) Sensitivity of mitochondrial transcription to different free radical species, Free Radical Biology & Medicine, 16, 323–329.
Kristal, B. S., B-J Park, B. P. Yu (1994) Antioxidants reduce peroxyl-radical mediated inhibition of mitochondrial transcription, Free Radical Biology & Medicine, 16, 653–660.
Kristal, B. S., J. D. Kim, B. P. Yu (1994) Tissue specific peroxyl radical mediated inhibition of mitochondrial transcription, Redox Report 1, 51–55.
Iwasaki, K., C.A. Gleiser, E.J. Masoro, C.A. McMahan, E.J. Seo, B.P. Yu (1988) The influence of dietary protein source in longevity and age-related disease processes of Fischer rats, The Journals of Gerontology, 43, B5–B12.
Kristal, B. S., B. K. Park, B. P. Yu (1996) 4-Hydroxyhexenal is potent inducer of the mitochondrial permeability transition, The Journal of Biological Chemistry, 271, 6033–6038.
Kristal, B. S., S. J. Koopmans, C. T. Jackson, Y. Ikeno, B-J Park, B. P. Yu (1997), Oxidant-mediated repression of mitochondrial transcription in diabetic rats, Free Radical Biology & Medicine, 22, 813–822.
Dixon, W. J. (1950) Analysis of extreme values, Annals of Mathematical Statistics, 21, 488–506.
Niki, E., Y. Yamamoto, E. Komuro, K. Sato (1991) Membrane damage due to lipid peroxidation, The American Journal of Clinical Nutrition, 53, 201S–205S.
Fernandez-Silva, P., V. Petruzzella, F. Fracasso, M. N. Gadaleta, P. Cantatore (1991) Reduced synthesis of mtRNA in isolated mitochondria or senescent rat brain, Biochemical and Biophysical Research Communications, 176, 645–653.
Chandrasekaran, K.; T. Giordano, D. R. Brady, J. Stoll, L. J. Martin, S. I. Rapoport (1994) Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease, Molecular Brain Research, 24, 336–340.
Vincent, F., M. Corral-Debrinski, M. Adolphe (1994) Transient mitochondrial transcript level decay in oxidatively stressed chondrocytes, Journal of Cellular Physiology, 158, 128–132.
Laganiere, S., B. P. Yu (1993) Modulation of membrane phospholipid fatty acid composition by age and food restriction, Gerontology, 39, 7–18.
Pieri, C. (1991) Food restriction slows down age-related changes in cell membrane parameters, Annals of the New York Academy of Sciences, 624, 353–362.
Goldstein, A. (1967) Biostatistics: An Introductory Text, The Macmillan Co., New York.
Author information
Authors and Affiliations
About this article
Cite this article
Krista, B.S., Yu, B.P. Dietary restriction augments resistance to oxidant-mediated inhibition of mitochondrial transcription. AGE 21, 1–6 (1998). https://doi.org/10.1007/s11357-998-0001-0
Issue Date:
DOI: https://doi.org/10.1007/s11357-998-0001-0