The impact of α-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice

Lee, Cheol Koo; Pugh, Thomas D.; Klopp, Roger G.; Edwards, Jode W.; Allison, David B.; Weindruch, Richard; Prolla, Tomas A.

doi:10.1016/j.freeradbiomed.2004.01.015

Cited by 121 publications

(86 citation statements)

References 89 publications

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“…Recently, a-lipoic acid was shown to have no effect on mouse lifespan (Lee et al 2004), however, in a separate study, a 12% increase in lifespan was observed when female Drosophila were treated from day 10 past eclosion (Bauer et al 2004). In this study, a-lipoic acid was identified in an Faccelerated screening assay_ in which age-dependent enhancer-trap lines were constructed that expressed tetanus toxin light chain as a lethal reporter.…”

Section: Pharmacological Interventions That Increase Lifespanmentioning

confidence: 90%

“…In the absence of reliable pharmacokinetics for model invertebrates, microarray and other techniques can be used to probe the effects of the compound. For example, in the mouse, a-lipoic acid treatment results in decreased expression of genes encoding molecular chaperones, the protein repair enzyme, protein-L-isoasparate methyltransferase, and some antioxidant functions including glutathione peroxidase 4 (Gpx4) and a cytosolic peroxiredoxin (Lee et al 2004). This illustrates that antioxidant treatment can result in gene expression changes likely to be detrimental for lifespan outweighing direct benefits of the antioxidant functions.…”

Section: The Need For Pharmacogenomicsmentioning

confidence: 99%

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Pharmacological intervention in invertebrate aging

Lithgow

Gill

Olsen

et al. 2005

AGE

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Prompted by successful genetic interventions in aging we now consider the utility of pharmacological interventions. A few clear cases of lifespan extension resulting from exposure to compounds suggest that aging can be slowed and that the pharmacology of lifespan extension is a feasible area for research. Compounds that slow aging may prompt the rational design of therapeutics against age-related diseases. Here we evaluate invertebrate models for drug discovery in aging and outline how the field may develop from these simple first steps.

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Section: Pharmacological Interventions That Increase Lifespanmentioning

confidence: 90%

Section: The Need For Pharmacogenomicsmentioning

confidence: 99%

Pharmacological intervention in invertebrate aging

Lithgow

Gill

Olsen

et al. 2005

AGE

View full text Add to dashboard Cite

show abstract

“…8). Two previous studies on mice and rats in other laboratories, in which CoQ 10 was administered at dosages lower than the highest dosage used by us, also reported no effect on life span (Lonnrot et al, 1998;Lee et al, 2004). Results of studies in other species are, however, quite contradictory and species-specific.…”

Section: Coq Intake Mitochondrial Function and Life Span In Micementioning

confidence: 51%

“…There is also no clear indication of its ability to influence the life span or brain function of mammals, however, it is conceivable that beneficial effects of CoQ 10 intake may occur under certain pathological conditions. It is also worth noting that CoQ 10 intake has been shown to broadly affect the pattern of gene expression (Lee et al, 2004;Groneberg et al, 2005), indicated by the abundance of mRNAs, however, the nature of the physiological impact remains to be demonstrated.…”

Section: Coq Intake and Brain Function In Micementioning

confidence: 99%

Coenzyme Q, oxidative stress and aging

2007

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Coenzyme Q (CoQ) has three well-characterized functions in mitochondria, namely (i) transfer of reducing equivalents in the electron transport chain, (ii) generation of superoxide anion radical (O 2˙̄) , and (iii) quenching of free radicals. The main purpose of this review is to discuss the effects of CoQ 10 intake for relatively prolonged periods on mitochondrial respiratory capacity, indicators of oxidative stress, and life span of animals, in context of the broader issue of whether or not the overall progression of the aging process can be modified by CoQ 10 administration. Comparative studies on different mammalian species have indicated that the rate of mitochondrial superoxide anion radical generation is directly correlated with mitochondrial CoQ 9 content and inversely related to amounts of CoQ 10 , particularly the CoQ 10 bound to mitochondrial membrane proteins. Contrary to the historical view, dietary supplementation of mice and rats with CoQ 10 has been demonstrated to augment the endogenous CoQ content (CoQ 9 + CoQ 10) in mitochondria and homogenates of various tissues, albeit to varying extent. Ingestion of CoQ 10 results in the elevation of endogenous CoQ 9 , the predominant homologue in mice and rats. In our studies, there was no indication of a discernable effect of CoQ 10 intake reflecting enhancement of mitochondrial respiratory activity, antioxidant capacity and pro-oxidant potentiation or prolongation of life span. The possibility that CoQ 10 intake affects certain other biological functions by as yet unelucidated mechanisms cannot be ruled out as CoQ has been shown to broadly alter gene expression in mice.

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“…Dietary supplementation as a means of delaying agerelated neural disorders is more likely to be adhered to than any regimen based on caloric restriction, which is known to retard aging processes. However, no dietary supplement has yet been found as effective as caloric restriction in extending life span [125]. The consumption of melatonin on a regular basis may help to mitigate some aspects of brain aging and appears to pose very little downside risk.…”

Section: Discussionmentioning

confidence: 99%

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.

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The impact of α-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice

Cited by 121 publications

References 89 publications

Pharmacological intervention in invertebrate aging

Pharmacological intervention in invertebrate aging

Coenzyme Q, oxidative stress and aging

Melatonin, Oxidative Stress, and the Aging Brain

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