Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 127, Issue 1, Pages 79-84Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2005.09.028
Keywords
citric acid cycle; aconitase; aging
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Funding
- NIA NIH HHS [R01 AG013563, R01 AG013563-13, R01 AG13563] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [R01AG013563] Funding Source: NIH RePORTER
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The activities of the citric acid cycle enzymes were determined in mitochondria isolated from kidneys of relatively young, middle age, and old mice. Aconitase exhibited the most significant decrease in activity with age. The activity of alpha-ketoglutarate dehydrogenase exhibited a modest decrease in activity, while NADP(+)-isocitrate dehydrogenase (NADP(+)-ICD) activity increased moderately with age. Activities of citrate synthase, NAD(+)-isocitrate dehydrogenase (NAD(+)-ICD), succinyl-CoA synthetase (SCS), succinate dehydrogenase (SD), fumarase (FUM), and malate dehydrogenase (MD) were not affected. The molar ratio of the intra-mitochondrial redox indicator, NADPH:NADP(+), was higher in young compared to old animals, while the NADH:NAD(+) molar ratio remained unchanged. It is suggested that an age-related decrease in aconitase activity along with relatively subtle alterations in activities of some other citric acid cycle enzymes are likely to contribute to a decline in the overall efficiency of mitochondrial bioenergetics. The biological consequences of such alterations include age-related fluctuations in the citric acid cycle intermediates, which are precursors of protein synthesis, activators of fatty acid synthesis, and can also act as ligands for orphan G-protein coupled receptors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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