Table 1.
Synopsis of major findings on age-related changes in cardiac mitochondrial bioenergetics, oxidant generation, and quality control
| Experimental Model | Parameter(s) Examined | Findings | Reference |
|---|---|---|---|
| Tg-Sirt1 mice | Effects of cardiac-specific Sirt1 overexpression on cardiac aging | Attenuation of age-dependent cardiac hypertrophy, apoptosis/fibrosis, oxidative stress, and heart dysfunction by low to moderate (2.5- to 7.5-fold) Sirt1 overexpression; worsening of mitochondrial dysfunction, oxidative stress, and cardiomyopathy by high levels (12.5-fold) of Sirt1 overexpression | Alcendor et al. (4) |
| Polg/mCAT mice | Effects of mtDNA mutations on age-dependent heart structure and function; effects of mCAT overexpression on PolG phenotype | Marked cardiac hypertrophy and dilation, impairment of systolic and diastolic function, increased cardiac fibrosis; increased mtDNA deletions and protein oxidative damage; increased expression of apoptotic and senescence markers; decline in mitochondrial biogenesis signaling; partial rescue of PolG phenotype by mCAT | Dai et al. 2010 (36) |
| mCAT mice | Effects of mCAT overexpression on indexes of cardiac aging | Attenuated age-related cardiac dysfunction; reduced mitochondrial protein oxidation and mtDNA mutations; protection against cardiac hypertrophy and heart failure | Dai et al. 2009 (38) |
| Fischer 344 rats | Oxidative metabolism in SSM and IFM from 6-, 24-, and 28-month-old rats | Decreased rate of oxidative phosphorylation and cytochromic c oxidase activity in IFM from aged rats; no changes in SSM | Fannin et al. 1999 (54) |
| Fischer 344 rats | H2O2 and oxidative damage in SSM and IFM from 6- and 24-month-old rats | Age-dependent increase in H2O2 production by SSM, not by IFM; increased oxidative stress (4-HNE-modified proteins, protein carbonyls, and MDA) in IFM from old rats, only protein carbonyls in aged SSM; oxidative stress more severe in IFM than in SSM; age-related increases in MnSOD, GPX, and CAT activities in IFM; increased MnSOD and GPX activities and declined CAT activity in aged SSM | Judge et al. 2005 (87) |
| PolG mice | Oxidative stress and apoptosis in mice with homozygous mutation of PolG | Accumulation of mtDNA mutations with no increases in oxidative stress in isolated cardiac mitochondria; accelerated cardiac aging | Kujoth et al. 2005 (99) |
| Fischer 344 rats | Oxidative stress and mitochondrial apoptotic signaling in the heart from 6-, 16-, and 24-month-old 344 rats | Age-associated increase in MnSOD and GPX activity; elevated cytosolic cytochrome c content and decreased mitochondrial Bcl-2 with age | Phaneuf et al. 2001 (155) |
| Fischer 344 rats | Mitochondrial antioxidant capacity, oxidant generation, and oxidative damage to complex IV in IFM and SSM from 2- to 5- and 24- to 28-month-old rats | Higher rates of oxidant production and decline in mitochondrial ascorbate levels and GSH redox status only in IFM from old rats; fourfold increase in 4-HNE-modification and loss of complex IV activity limited to IFM from old rats | Suh et al. 2003 (175) |
| mCAT mice | Effects of mCAT overexpression on indexes of cardiac aging | Delayed cardiac aging, lower oxidative damage, H2O2 production and H2O2-induced aconitase inactivation, reduced mtDNA deletions; 18% lifespan extension | Schriner et al. 2005 (166) |
| PolG mice | Impact of homozygous mutation of PolG on mouse aging | Accumulation of cardiac mtDNA mutations associated with multiple signs of accelerated aging and reduced lifespan | Trifunovic et al. 2004 (186) |
| Cardiac-specific Atg5-deficient mice | Age-associated changes in autophagy in WT mouse heart; cardiac function and lifespan in Atg5-deficient mice | Reduction in the autophagy marker LC3-II with age; LV enlargement and decreased fractional shortening in Atg5-deficient mice; disorganized sarcomere structure and collapsed mitochondria with impaired respiration in Atg5-deficient mice | Taneike et al. 2010 (180) |
4-HNE, 4-hydroxynonenal; CAT, catalase; GPX, glutathione peroxidase; GSH, glutathione; IFM, intermyofibrillar mitochondria; LC3, light chain 3; mCAT, catalase targeted to the mitochondrial matrix; MDA, malondialdehyde; MnSOD, manganese-dependent superoxide dismutase; PolG, mtDNA polymerase-γ; SSM, subsarcolemmal mitochondria; Tg-Sirt1, Sirt1 transgenic; WT, wild-type.