Mitochondrial DNA Transcription and Translation in Aged Rat

Gadaleta, Maria Nicola; Petruzzella, Vittoria; Daddabbo, L.; Olivieri, Claudiana; Fracasso, Flavio; Polosa, Paola Loguercio; Cantatore, Palmiro

doi:10.1111/j.1749-6632.1994.tb12082.x

Cited by 37 publications

(14 citation statements)

References 32 publications

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“…The content of mtRNA normalizes in the aged heart after treatment secondary to increased RNA synthesis (32,33). The increase in mtRNA synthesis leads to increased mitochondrial protein synthesis (chloramphenicol sensitive; ref 32), with increased content of mitochondrial-encoded electron transport subunits after acetylcarnitine treatment (32). Based on the increases seen in the contents of cytochrome aa 3 and b in the present study, it appears that stimulation of mitochondrial protein synthesis contributes to acetylcarnitine-mediated improvement in respiration in the aged heart.…”

Section: Discussionmentioning

confidence: 96%

“…However, despite the aging-related membrane defect in IFM (8, 13), aging does not decrease the content of cardiolipin in either SSM or IFM in the aged Fischer 344 rat heart (16). Second, treatment with acetylcarnitine increases transcription of mitochondrial DNA (mtDNA) in the aged heart in a dose-and time-dependent manner (32). The optimal response to acetylcarnitine occurs at 3 h and 300 mg/kg, the treatment regimen used in the current study.…”

Section: Discussionmentioning

confidence: 97%

“…The optimal response to acetylcarnitine occurs at 3 h and 300 mg/kg, the treatment regimen used in the current study. The content of mtRNA normalizes in the aged heart after treatment secondary to increased RNA synthesis (32,33). The increase in mtRNA synthesis leads to increased mitochondrial protein synthesis (chloramphenicol sensitive; ref 32), with increased content of mitochondrial-encoded electron transport subunits after acetylcarnitine treatment (32).…”

Section: Discussionmentioning

confidence: 99%

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Reversal of mitochondrial defects before ischemia protects the aged heart

Lesnefsky

Moghaddas

et al. 2006

FASEB j.

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Myocardial injury is increased in the aged heart during ischemia and reperfusion. Aging decreases oxidative metabolism in interfibrillar mitochondria (IFM) located between the myofibrils. We asked whether reversal of aging defects in IFM before ischemia would decrease injury in the aged heart following ischemia and reperfusion. Treatment with acetylcarnitine (AcCN) increases the activity of cytochrome oxidase in the aged heart. Aged (24 months) and adult (6 months) Fischer 344 rats were treated with AcCN (300 mg/kg i.p. 3 h before excision of the heart) or served as controls. AcCN restored oxidative phosphorylation and the activity of complexes III and IV in IFM from aged hearts to rates present in adults. Isolated hearts underwent 25 min global ischemia and 30 min reperfusion without additional treatment. Contractile recovery during reperfusion improved in hearts from AcCN-treated aged rats compared to aged controls and were similar to adults in recovery. AcCN-treated aged hearts sustained less damage, indicated by decreased lactate dehydrogenase (LDH) release during reperfusion. AcCN treatment did not alter functional recovery or LDH release in adults. Restoration of mitochondrial function in the aged heart before ischemia was accompanied by enhanced contractile recovery and decreased tissue injury following ischemia and reperfusion.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Reversal of mitochondrial defects before ischemia protects the aged heart

Lesnefsky

Moghaddas

et al. 2006

FASEB j.

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“…Furthermore, aging affects the expression of genes encoding mitochondrial proteins, evidenced by decreased messenger RNA transcript levels [12][13][14]. An age-related decline in the rate of protein synthesis [9,15,16] and proteolytic activity [17] is also reported in different aged tissues and organisms. Importantly, decreased protein turnover may lead to accumulation of oxidatively damaged dysfunctional proteins, such as carbonylated [18,19], nitrotyrosine-modified [20] and cysteine-oxidized proteins [21].…”

Section: Introductionmentioning

confidence: 96%

Rat liver mitochondrial proteome: Changes associated with aging and acetyl-L-carnitine treatment

Musicco

Capelli

Pesce

et al. 2011

Journal of Proteomics

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“…Instead of permanent mitochondrial damage, Paradies et al [11,12] have shown that pharmacological supplementation of senescent ad libitum fed rats with acetyl-Lcarnitine (ALCAR) two orders of magnitude (intravenous 100-300 mg ALCAR/kg animal weight) above normal blood levels can temporarily restore youthful maximal (state 3) and youthful resting (state 4) energy production within a few hours [13]. Intravenous or oral pharmacological levels of ALCAR have wide-ranging benefits [14] and extremely low toxicity in both rats and humans, roughly comparable to amino acids.…”

Section: Declined Reserve Capacitymentioning

confidence: 99%

Insulin Exposure and Unifying Aging

Parr

1999

Gerontology

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Background: Absence of a widely agreed upon central paradigm for mammalian aging. Objective: Detailed elaboration of a proposed mammalian aging paradigm. Methods: Elaboration of a new theoretical model. Results: Hormonal imbalance-growth factor exposure theory (HI-GFE theory) can account for two major aging phenomena: (1) decline in mammalian ‘reserve capacity’ and consequent rise of diseases of maintenance, and (2) rise then peaking of most age-associated proliferative diseases. Reserve capacity decline via gradual decline in mitochondrial maximal energy production (state 3) accounts for the gradual redirection of declined maximal energy production toward survival functions like ion pumping to the relative detriment of RNA and protein synthesis as seen in lesser synthetic rates and slower turnover with consequent gradual cellular impairment. Developmental program triggered, and over-ample nutritionally driven, growth factor exposure in youth to middle age encourages promotional events that lead to proliferative diseases that rise coincident to rapidly declining reserve capacity and cumulative increased mutational status of age. Conclusions: Declining mitochondrial state 3 aging energy production status is easily and safely reversible with probable consequences of greatly postponing the decline in overall ‘reserve capacity’ which may also improve insulin: growth hormone balance and result in lower overall growth factor exposure and consequent longer healthy life of a potentially greater magnitude increase in life spans than that seen in calorie-restricted animals.

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Mitochondrial DNA Transcription and Translation in Aged Rat

Cited by 37 publications

References 32 publications

Reversal of mitochondrial defects before ischemia protects the aged heart

Reversal of mitochondrial defects before ischemia protects the aged heart

Rat liver mitochondrial proteome: Changes associated with aging and acetyl-L-carnitine treatment

Insulin Exposure and Unifying Aging

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