Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats

被引：18

作者：

Chimienti, Guglielmina ^{[1
]}

Picca, Anna ^{[2
,3
]}

Fracasso, Flavio ^{[1
]}

Marzetti, Emanuele ^{[3
]}

Calvani, Riccardo ^{[2
,3
]}

Leeuwenburgh, Christiaan ^{[4
]}

Russo, Francesco ^{[5
]}

Lezza, Angela Maria Serena ^{[1
]}

Pesce, Vito ^{[1
]}

机构：

[1] Univ Bari Aldo Moro, Dept Biosci Biotechnol & Biopharmaceut, I-70125 Bari, Italy

[2] Univ Cattolica Sacro Cuore, Lgo A Gemelli 1, I-00168 Rome, Italy

[3] Fdn Policlin Univ Agostino Gemelli IRCCS, Lgo F Vito 8, I-00168 Rome, Italy

[4] Univ Florida, Div Biol Aging, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA

[5] Natl Inst Gastroenterol S de Bellis, Lab Nutr Pathophysiol, I-70013 Castellana Grotte, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 10期

关键词：

rat liver; longevity; mtDNA content; mtDNA common deletion; TFAM binding; 8-oxodG incidence; MITOCHONDRIAL TRANSCRIPTION INITIATION; HEAVY-STRAND PROMOTER; DNA COPY NUMBER; SKELETAL-MUSCLE; F344BNF1-HYBRID RATS; CALORIE RESTRICTION; BIOGENESIS; QUANTITATION; EXPRESSION; LONGEVITY;

D O I：

10.3390/ijms20102601

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

While mitochondrial dysfunction is acknowledged as a major feature of aging, much less is known about the role of mitochondria in extended longevity. Livers from aged (28-month-old) and extremely aged (32-month-old) rats were analyzed for citrate synthase activity, mitochondrial transcription factor A (TFAM) amount, mitochondrial DNA (mtDNA), and 4.8 Kb common deletion contents. None of the assayed parameters differed significantly between age groups. TFAM-binding to mtDNA and the incidence of 8-oxo-deoxyguanosine in specific mtDNA regions, encompassing the origins of mtDNA replication (D-loop and Ori-L) and the 16-bp long direct repeat 1 (DR1) of the 4.8 Kb deletion, were determined. A decrease in TFAM binding was unveiled at all regions in extremely aged in comparison with aged rats. Reduced incidence of oxidized purines at all assayed regions was detected in 32-month-old rats compared with the 28-month-old group. A significant positive correlation between the incidence of 8-oxo-deoxoguanosine and TFAM-bound mtDNA was found at D-Loop and Ori-L regions only in 28-month-old rats. The absence of such correlation in 32-month-old rats indicates a different, fine-tuned regulation of TFAM binding in the two age groups and supports the existence of two different paces in aging and extended aging.

引用

页数：13

共 44 条

[1] Elevated caspase and AIF gene expression correlate with progression of sarcopenia during aging in male F344BN rats [J].

Baker, David J. ;

Hepple, Russell T. .

EXPERIMENTAL GERONTOLOGY, 2006, 41 (11) :1149-1156

[2]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[3] Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number [J].

Campbell, Christopher T. ;

Kolesar, Jill E. ;

Kaufman, Brett A. .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2012, 1819 (9-10) :921-929

[4] Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA repair enzymes acting on free radical lesions [J].

Caston, Rachel Audrey ;

Demple, Bruce .

FREE RADICAL BIOLOGY AND MEDICINE, 2017, 107 :146-150

[5] Increased TFAM binding to mtDNA damage hot spots is associated with mtDNA loss in aged rat heart [J].

Chimienti, Guglielmina ;

Picca, Anna ;

Sirago, Giuseppe ;

Fracasso, Flavio ;

Calvani, Riccardo ;

Bernabei, Roberto ;

Russo, Francesco ;

Carter, Christy S. ;

Leeuwenburgh, Christiaan ;

Pesce, Vito ;

Marzetti, Emanuele ;

Lezza, Angela Maria Serena .

FREE RADICAL BIOLOGY AND MEDICINE, 2018, 124 :447-453

[6] Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans [J].

De Benedictis, G ;

Rose, G ;

Carrieri, G ;

De Luca, M ;

Falcone, E ;

Passarino, G ;

Bonafé, M ;

Monti, D ;

Baggio, G ;

Bertolini, S ;

Mari, D ;

Mattace, R ;

Franceschi, C .

FASEB JOURNAL, 1999, 13 (12) :1532-1536

[7] DETECTION AND QUANTITATION BY COMPETITIVE PCR OF AN AGE-ASSOCIATED INCREASE IN A 4.8-KB DELETION IN RAT MITOCHONDRIAL-DNA [J].

EDRIS, W ;

BURGETT, B ;

STINE, OC ;

FILBURN, CR .

MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING, 1994, 316 (02) :69-78

[8] MITOCHONDRIAL-DNA COPY NUMBER AND MITOCHONDRIAL-DNA DELETION IN ADULT AND SENESCENT RATS [J].

GADALETA, MN ;

RAINALDI, G ;

LEZZA, AMS ;

MILELLA, F ;

FRACASSO, F ;

CANTATORE, P .

MUTATION RESEARCH, 1992, 275 (3-6) :181-193

[9]

Gondo Y., 2016, Encyclopedia of Geropsychology, P2227, DOI [10.1007/978-981-287-080-3_182-1, DOI 10.1007/978-981-287-080-3_182-1, 10.1007/978-981-287-080-3182-1, DOI 10.1007/978-981-287-080-3182-1]

[10] Skeletal muscle aging in F344BNF1-hybrid rats:: I.: Mitochondrial dysfunction contributes to the age-associated reduction in VO2max [J].

Hagen, JL ;

Krause, DJ ;

Baker, DJ ;

Fu, MH ;

Tarnopolsky, MA ;

Hepple, RT .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2004, 59 (11) :1099-1110

← 1 2 3 4 5 →