PMID- 22945739
OWN - NLM
STAT- MEDLINE
DCOM- 20140520
LR  - 20211021
IS  - 1574-4647 (Electronic)
IS  - 0161-9152 (Print)
IS  - 0161-9152 (Linking)
VI  - 35
IP  - 5
DP  - 2013 Oct
TI  - Age- and calorie restriction-related changes in rat brain mitochondrial DNA and 
      TFAM binding.
PG  - 1607-20
LID - 10.1007/s11357-012-9465-z [doi]
AB  - Aging markedly affects mitochondrial biogenesis and functions particularly in 
      tissues highly dependent on the organelle's bioenergetics capability such as the 
      brain's frontal cortex. Calorie restriction (CR) diet is, so far, the only 
      intervention able to delay or prevent the onset of several age-related 
      alterations in different organisms. We determined the contents of mitochondrial 
      transcription factor A (TFAM), mitochondrial DNA (mtDNA), and the 4.8-kb mtDNA 
      deletion in the frontal cortex from young (6-month-old) and aged (26-month-old), 
      ad libitum-fed (AL) and calorie-restricted (CR), rats. We found a 70 % increase 
      in TFAM amount, a 25 % loss in mtDNA content, and a 35 % increase in the 4.8-kb 
      deletion content in the aged AL animals with respect to the young rats. 
      TFAM-specific binding to six mtDNA regions was analyzed by mtDNA 
      immunoprecipitation and semiquantitative polymerase chain reaction (PCR), showing 
      a marked age-related decrease. Quantitative real-time PCR at two subregions 
      involved in mtDNA replication demonstrated, in aged AL rats, a remarkable 
      decrease (60-70 %) of TFAM-bound mtDNA. The decreased TFAM binding is a novel 
      finding that may explain the mtDNA loss in spite of the compensatory TFAM 
      increased amount. In aged CR rats, TFAM amount increased and mtDNA content 
      decreased with respect to young rats' values, but the extent of the changes was 
      smaller than in aged AL rats. Attenuation of the age-related effects due to the 
      diet in the CR animals was further evidenced by the unchanged content of the 
      4.8-kb deletion with respect to that of young animals and by the partial 
      prevention of the age-related decrease in TFAM binding to mtDNA.
FAU - Picca, Anna
AU  - Picca A
AD  - Department of Biosciences, Biotechnologies and Pharmacological Sciences, 
      University of Bari, Via Orabona, 4, 70125, Bari, Italy.
FAU - Fracasso, Flavio
AU  - Fracasso F
FAU - Pesce, Vito
AU  - Pesce V
FAU - Cantatore, Palmiro
AU  - Cantatore P
FAU - Joseph, Anna-Maria
AU  - Joseph AM
FAU - Leeuwenburgh, Christiaan
AU  - Leeuwenburgh C
FAU - Gadaleta, Maria Nicola
AU  - Gadaleta MN
FAU - Lezza, Angela Maria Serena
AU  - Lezza AM
LA  - eng
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - R01 AG017994/AG/NIA NIH HHS/United States
GR  - 1 P30 AG028740/AG/NIA NIH HHS/United States
GR  - R01 AG17994/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120904
PL  - Netherlands
TA  - Age (Dordr)
JT  - Age (Dordrecht, Netherlands)
JID - 101250497
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Tfam protein, rat)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Aging/*genetics/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - *Caloric Restriction
MH  - Cerebral Cortex/metabolism
MH  - DNA Damage
MH  - DNA Replication
MH  - DNA, Mitochondrial/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Frontal Lobe/*metabolism
MH  - Gene Deletion
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Transcription Factors/genetics/*metabolism
PMC - PMC3776104
EDAT- 2012/09/05 06:00
MHDA- 2014/05/21 06:00
PMCR- 2014/10/01
CRDT- 2012/09/05 06:00
PHST- 2012/04/26 00:00 [received]
PHST- 2012/07/27 00:00 [accepted]
PHST- 2012/09/05 06:00 [entrez]
PHST- 2012/09/05 06:00 [pubmed]
PHST- 2014/05/21 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 9465 [pii]
AID - 10.1007/s11357-012-9465-z [doi]
PST - ppublish
SO  - Age (Dordr). 2013 Oct;35(5):1607-20. doi: 10.1007/s11357-012-9465-z. Epub 2012 
      Sep 4.