Mitochondrial oxidative stress in aging and healthspan

Dai, Dao-Fu; Chiao, Ying Ann; Marcinek, David J; Szeto, Hazel H; Rabinovitch, Peter S

doi:10.1186/2046-2395-3-6

Longevity & Healthspan

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]
	Polg^m/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]
	p66^shc	Targeted mutation of the p66^Shc 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
	SIRT3^-/-	SIRT3-deficient mice	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]

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