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Table 1 Mitochondrial targeted genetic and pharmacological manipulations on aging and healthspan

From: Mitochondrial oxidative stress in aging and healthspan

  Animal models Description Aging phenotypes Healthspan phenotypes
Genotypes mCAT Overexpression of catalase targeted to mitochondria 18% extension of lifespan [17]. Attenuated cardiac aging [43], aging-related sarcopenia [17], presbyacusis [44], and cancer incidence [45]. Protect against cardiac hypertophy and heart failure [46]
Reduce Aβ toxicity and oxidative injury, and extends the lifespan of Aβ PP overexpressing mice [47]
Protective against mitochondrial ROS production and subsequent dopaminergic neuron degeneration in MPTP-induced Parkinson’s disease model [48]
Attenuate lipid-induced insulin resistance in skeletal muscle [49]
Polgm/m Homozygous mutation of mitochondrial polymerase gamma D257A ‘Accelerated aging’: sarcopenia, graying and alopecia, kyphosis, presbyacusis, anemia [22, 23], age-dependent cardiomyopathy [25] Aggravate heart failure in response to Angiotensin II [46]
p66shc Targeted mutation of the p66Shc gene Extension of lifespan. Reduction of ROS and apoptosis [19] Attenuate Angiotensin II induced LV hypertrophy and cardiomyocytes apoptosis; reduce oxidative damage in cardiac progenitor cells, cardiomyocytes and endothelial cells in diabetes [19, 21, 50, 51]
SIRT3-/- SIRT3-deficient mice Accelerated cardiac aging, age-dependent increase in mitochondrial swelling due to increased mPTP opening [52] Early-age onset of hypertrophy associated with fibrosis
Abolish CR effect in reduction of oxidative damage, protection of cochlear neurons and prevention of presbycusis [53] Increased mortality after transverse aortic constriction [52]
Pharmacological treatments SS-31 Mitochondrial protective tetrapeptide Reverse age-related muscle weakness and muscle energy deficits [54] Attenuation of Angiotensin II induced cardiac hypertrophy and Gαq overexpression induced heart failure [55]
Ameliorate cardiac dysfunction after tranverse aortic constriction [56]
Improve systolic function ischemic HF model [57, 58]
Attenuate cardiac I/R injury [59, 60]
Protect against renal I/R injury [61]
Prevent high fat diet induced insulin resistance in skeletal muscle [62]
Attenuation of diabetic retinopathy [63]
Protective against ALS in SOD1 mutant mice [64] and Parkinson’s diseases in MPTP model [65]
MitoQ Ubiquinone (antioxidant) conjugated with TPP+   Reduction of blood pressure and cardiac hypertrophy in spontaneous hypertensive rats [66]
SkQ Plastoquinone conjugated with TPP+ Prolonged lifespan. Attenuation of age-related decline in immunity. Protective against baldness and lordokyphosis in aged mice [18, 67] Attenuate heart arrhythmia, I/R injury, myocardial infarction, and kidney ischemia [68]
Delayed tumor development in p53-deficient mice [30]
Protect against cataract and retinopathy in OXYS rats [69]