Lowered rates of protein synthesis by mitochondria isolated from organisms of increasing age

Bailey, P.J.; Webster, George C.

doi:10.1016/0047-6374(84)90074-5

Cited by 36 publications

(12 citation statements)

References 20 publications

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“…However, the percentage of mitochondrial to mixed muscle protein synthesis rate was also decreased with aging, indicating a more pronounced fall in mitochondrial synthesis than the average decline in synthesis rate of all muscle proteins. Decreased protein synthesis rates of mitochondria with aging have been reported in lower organisms (Drosophila) and in liver and kidney of small mammals (10,11). In contrast, mitochondrial protein synthesis was not decreased in rat liver, testes, heart, brain, intestinal mucosa, lung, and kidney with aging (36).…”

Section: Discussionmentioning

confidence: 99%

“…An age-related increase in mtDNA mutations may, therefore, lead to an overall decreased synthesis of mitochondrial protein or result in synthesis of abnormal proteins, causing impairment of enzyme activities and mitochondrial functions. In vitro experiments in mitochondria isolated from different animal tissues have shown that a decreased protein synthesis rate occurs with aging (10,11). In vivo measurements of the rate of muscle mitochondrial protein synthesis have not been performed in humans.…”

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confidence: 99%

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Effect of age onin vivorates of mitochondrial protein synthesis in human skeletal muscle

Rooyackers

Adey

Ades

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

519

393

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A progressive decline in muscle performance in the rapidly expanding aging population is causing a dramatic increase in disability and health care costs. A decrease in muscle endurance capacity due to mitochondrial decay likely contributes to this decline in muscle performance. We developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using needle biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and function of skeletal muscle. The fractional rate of muscle mitochondrial protein synthesis in young humans (24 ؎ 1 year) was 0.081 ؎ 0.004%⅐h ؊1 , and this rate declined to 0.047 ؎ 0.005%⅐h ؊1 by middle age (54 ؎ 1 year; P < 0.01). No further decline in the rate of mitochondrial protein synthesis (0.051 ؎ 0.004%⅐h ؊1 ) occurred with advancing age (73 ؎ 2 years). The mitochondrial synthesis rate was about 95% higher than that of mixed protein in the young, whereas it was approximately 35% higher in the middle-aged and elderly subjects. In addition, decreasing activities of mitochondrial enzymes were observed in muscle homogenates (cytochrome c oxidase and citrate synthase) and in isolated mitochondria (citrate synthase) with increasing age, indicating declines in muscle oxidative capacity and mitochondrial function, respectively. The decrease in the rates of mitochondrial protein synthesis is likely to be responsible for this decline in muscle oxidative capacity and mitochondrial function. These changes in muscle mitochondrial protein metabolism may contribute to the age-related decline in aerobic capacity and muscle performance.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of age onin vivorates of mitochondrial protein synthesis in human skeletal muscle

Rooyackers

Adey

Ades

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

519

393

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“…Early experiments measured mitochondrial protein synthesis rates in vitro from the incorporation of radiolabelled amino acid tracers in isolated mitochondria. Such experiments in Drosophila, mice, and rat tissues revealed that the synthesis rates of mitochondrial proteins decreased with advancing age of the organism (Marcus et al, 1982a; Marcus et al, 1982b; Bailey and Webster, 1984). In 1996, Rooyackers et al used stable isotopes of amino acids to measure the in vivo synthesis rates of mitochondrial proteins in human skeletal muscle (Figure 3a-c) (Rooyackers et al, 1996).…”

Section: Changes In Mitochondrial Function With Agingmentioning

confidence: 99%

Mitochondrial DNA alterations and reduced mitochondrial function in aging

Hebert

Lanza

Nair

2010

Mechanisms of Ageing and Development

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Oxidative damage to mitochondrial DNA increases with aging. This damage has the potential to affect mitochondrial DNA replication and transcription which could alter the abundance or functionality of mitochondrial proteins. This review describes mitochondrial DNA alterations and changes in mitochondrial function that occur with aging. Age-related alterations in mitochondrial DNA as a possible contributor to the reduction in mitochondrial function are discussed.

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“…Most of this decrease occurred within the first 14 days of adult life. Interestingly enough, subsequent data showed that this decrease in protein synthesis did not take place uniformly throughout the body; the head, thorax, and abdomen showed decreases of 15%, 95%, and 33%, respectively, 79 and there were different rates of decrease in the mitochondria as compared to the rest of the cell 80 . Thus the decrease in protein synthesis is tissue‐ and stage‐specific, although the meaning of the tissue specificity is not yet clear.…”

Section: Testing Of Aging Theories: What Do We Know About the Mechanimentioning

confidence: 99%

“…Also note that there appears to be no effect on the transcriptional activity of the other genes assayed. (Redrawn from Webster , 80 – 81 with permission.)…”

Section: Testing Of Aging Theories: What Do We Know About the Mechanimentioning

confidence: 99%

Review of Genetic Investigations into the Aging Processes of Drosophila

Arking¹,

Dudas²

1989

J American Geriatrics Society

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The field has progressed to the point where a genetic investigation of the aging processes in Drosophila can be viewed as constituting both a serious and a feasible research program. There now exists at least one single gene mutant which yields an accelerated aging phenotype, at least two single gene null mutants affecting enzymes implicated in regulating the aging process and resulting in premature death, and at least two strains created by artificial selection which produce extended-longevity phenotypes. In addition, genes such as adh have an indirect and interactive effect upon the animal's longevity and might also play an important role in the genetic regulation of this process. Although far from complete, some essential tools are now in place and are being used to answer some of the questions posed by Martin. Of the several theories put forth to explain aging in Drosophila, it appears as if the data best uphold the free radical and the protein synthesis/gene expression theories. It is entirely possible that these two theories are complementary aspects of a broader underlying process. The genetic mechanisms controlling these physiological processes clearly do so in concert with certain environmental factors. The net effect of their interactions may be the decreased synthetic and repair ability of the cell as suggested by Lamb and by Webster. It is probably true that aging and longevity are multicausal phenotypes. Our only hope of understanding such a complex phenotype is to dissect it genetically, one (or a few) genes at a time under rigidly controlled conditions. Thorough genetic description of each system will be the prerequisite to their molecular analysis. This will likely result in multiple explanations, ideally one for each system. Yet these multiple molecular genetic explanations may well enable us to see some commonality underlying the aging process in this organism. The fact that several different lines of evidence appear to be converging on a small number of theoretical explanations is an encouraging sign. We should also be heartened by the extraordinary increase in our knowledge of embryonic development in Drosophila as a result of just such a strategy. And we should not forget that the homeotic mutants which now play such a large role in the deciphering of embryogenesis were once classified as "complex loci" and that the then-accepted explanations gave no hint of the underlying molecular relationships. For now it is fair to conclude that aging in Drosophila may be viewed as a genetically-determined, environmentally-modulated, event-dependent process.(ABSTRACT TRUNCATED AT 400 WORDS)

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Lowered rates of protein synthesis by mitochondria isolated from organisms of increasing age

Cited by 36 publications

References 20 publications

Effect of age onin vivorates of mitochondrial protein synthesis in human skeletal muscle

Effect of age onin vivorates of mitochondrial protein synthesis in human skeletal muscle

Mitochondrial DNA alterations and reduced mitochondrial function in aging

Review of Genetic Investigations into the Aging Processes of Drosophila

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