Aging affects mitochondria in a tissue-specific manner and to date only calorie restriction (CR) is able to delay or prevent the onset of several age-related changes also in mitochondria. Mitochondrial Transcription Factor A (TFAM) is considered the histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome including modulation of transcription, regulation of copy number and maintenance of mtDNA as well as constitution of mtDNA nucleoids. We used samples of frontal cortex and soleus skeletal muscle from 6- and 26-month-old ad libitum-fed and 26-month-old calorie-restricted rats and of livers from 18- and 28-month-old ad libitum-fed and 28-month-old calorie-restricted rats to determine TFAM amount, TFAM-binding to mtDNA and mtDNA content. We found an age-related increase in TFAM amount in frontal cortex, not affected by CR, versus an age-related decrease in soleus and liver, fully prevented by CR. The semi-quantitative analysis of in vivo binding of TFAM to specific mtDNA regions, by mtDNA immunoprecipitation assay, showed a marked age-dependent decrease in TFAM-binding activity in the frontal cortex, partially prevented by CR. Instead, an age-related increase in TFAM-binding to mtDNA, fully prevented by CR, was found in the soleus and liver. MtDNA content showed a common age-related decrease, completely prevented by CR in soleus and liver, but not in frontal cortex. We highlight for the first time a trend shared by skeletal muscle and liver, but not by the frontal cortex counterpart, in some relevant changes induced by aging and CR in mitochondria. Such trend involves the modulation of TFAM expression, TFAM-binding to mtDNA and mtDNA content and supports the existence of similar mitochondrial molecular mechanisms in skeletal muscle and liver but not in frontal cortex. Modulation of TFAM-binding to mtDNA, affecting mtDNA functions, appears to contribute to the tissue-specific alterations of mitochondrial biogenesis during aging as well as CR.

Age- and calorie restriction-related changes in TFAM amount and binding to mtDNA and mtDNA content share a common trend in skeletal muscle and liver, but not in the frontal cortex counterpart.

PESCE, VITO;LEZZA, Angela Maria Serena
2014

Abstract

Aging affects mitochondria in a tissue-specific manner and to date only calorie restriction (CR) is able to delay or prevent the onset of several age-related changes also in mitochondria. Mitochondrial Transcription Factor A (TFAM) is considered the histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome including modulation of transcription, regulation of copy number and maintenance of mtDNA as well as constitution of mtDNA nucleoids. We used samples of frontal cortex and soleus skeletal muscle from 6- and 26-month-old ad libitum-fed and 26-month-old calorie-restricted rats and of livers from 18- and 28-month-old ad libitum-fed and 28-month-old calorie-restricted rats to determine TFAM amount, TFAM-binding to mtDNA and mtDNA content. We found an age-related increase in TFAM amount in frontal cortex, not affected by CR, versus an age-related decrease in soleus and liver, fully prevented by CR. The semi-quantitative analysis of in vivo binding of TFAM to specific mtDNA regions, by mtDNA immunoprecipitation assay, showed a marked age-dependent decrease in TFAM-binding activity in the frontal cortex, partially prevented by CR. Instead, an age-related increase in TFAM-binding to mtDNA, fully prevented by CR, was found in the soleus and liver. MtDNA content showed a common age-related decrease, completely prevented by CR in soleus and liver, but not in frontal cortex. We highlight for the first time a trend shared by skeletal muscle and liver, but not by the frontal cortex counterpart, in some relevant changes induced by aging and CR in mitochondria. Such trend involves the modulation of TFAM expression, TFAM-binding to mtDNA and mtDNA content and supports the existence of similar mitochondrial molecular mechanisms in skeletal muscle and liver but not in frontal cortex. Modulation of TFAM-binding to mtDNA, affecting mtDNA functions, appears to contribute to the tissue-specific alterations of mitochondrial biogenesis during aging as well as CR.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/102684
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