Table 1.

Animal models of cardiovascular aging

Model	Relevance to aging	Cardiovascular phenotype	Refs.
1. Natural aging
Aged C57BL/6J mice		Cardiac hypertrophy and dysfunction, enhanced fibrosis, aortic stiffness	[217,218]
Aged Fischer 344 rats		LV hypertrophy, diastolic dysfunction, abdominal aorta with decreased sodium nitroprusside-mediated relaxation	[219,220]
Aged Fischer 344/Brown Norway F1 rats		LV dilatation, mild hypertrophy, fibrosis, LV diastolic and systolic dysfunction	[221]
Aged Rhesus macaque (Macaca mulatta)		Myocardial fibrosis, cardiac hypertrophy, aortic valve calcification	[146]
2. Premature aging
Senescence-accelerated prone (SAMP) mice	Selective inbreeding of AKR/J mice with inherited senescence	Cardiac diastolic dysfunction, cardiac fibrosis, vascular dysfunction	[148,222]
Mus musculus castaneus (CAST)	Mice with short telomeres from birth	Cardiac dysfunction, hypertrophy, fibrosis and senescence	[149]
3. Chemically induced aging
D-galactose-induced aging in mice and rats	D-galactose treatment increases the levels of senescence-associated β-galactosidase (SA-β-gal)	Increase in heart weight, cardiac hypertrophy, cardiac fibrosis and LV dysfunction	[150]
4. Progeria models
LmnaG609G/G609G mice	LMNA point mutation (G609G) that activates a cryptic donor splice site and produces progerin, a truncated form of prelamin A	Hutchinson-Gilford progeria syndrome (HGPS), cardiac fibrosis, electrocardiographic alterations, cardiac diastolic dysfunction, HFpEF	[157]
LmnaN195K/N195K mice	LMNA missense mutation (N195K) in lamins A and C	Dilated cardiomyopathy with conduction system disease	[223]
LmnaH222P/H222P mice	LMNA missense mutation (H222P) identified in a family with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD)	EDMD, DCM	[224]
Hypomorphic BubR1 mutant(BubR1H/H) mice	Reduced expression of spindle assembly checkpoint kinase BubR1, leading to chromosome number instability	Cardiac arrhythmias, arterial wall stiffening	[225,226]
5. Mitochondrial mutations
Cardiac-specific termed Y955C Polg mutant mice	Polg point mutation (Y955C) leading to mtDNA depletion	LV hypertrophy, increased ventricular volume	[160,227]
D257A Polg mutant mice	Polg mutation (D257A) in the N-terminal "proofreading” exonuclease domain, resulting in a protein without polymerase proofreading function in mitochondria	Biventricular hypertrophy, fibrosis, heart failure, arterial stiffening	[161,228]
Tafazzin-deficient mice	Mice lacking tafazzin, a mitochondrial transacylase essential for cardiolipin remodeling	Barth syndrome, LV dilation, reduced ejection fraction	[229]
heart/muscle-specific Mn-SOD-deficient mice (H/M-Sod2−/−)	Mice with a specific in the heart and skeletal muscle loss of manganese superoxide dismutase (Mn-SOD) expression, a principal scavenger enzyme in mitochondrial matrix	Dilated cardiomyopathy, reduced cardiac contractility	[230]
6. Other global gene mutations
Klotho-deficient (KL−/−) mice	Knock-out of Klotho	Impaired cardiac function, increased heart size, increased LV myocardial mass	[57]
G5 telomerase-deficient (telomerase RNA component, TERC−/−) mice	Telomerase-deficient mice after G3 generation have short telomeres, aneuploidy, and end-to-end chromosome fusions	Pathological cardiac remodeling, severe ventricular dysfunction	[231,232]
Pim triple knock-out mice (Pim1, Pim2 −/− and Pim3 −/−)	Mice lacking Pim kinases, which are highly conserved serine/threonine kinases, have altered mitochondrial morphology	Cardiac hypertrophy, heart failure, cardiac fibrosis	[233]
Interleukin-10 knockout IL-10(tm/tm) mice	Mice lacking IL-10, which is an anti-inflammatory cytokine	Stiffer vessels, reduced vascular relaxation, asymmetric hypertrophy, systolic and diastolic dysfunction	[234]
DNA-helicase-regulatory protein (WRN) WRN-K577M mutant mice	Amino acid substitution of WRN at position 577 eliminates the ATPase and helicase activity	Werner syndrome, diastolic LV dysfunction, cardiac fibrosis and hypertrophy	[235]

homozygous mutation in the encoding domain (D257A) of a proofreading deficient version of Polg develop biventricular hypertrophy at 10–12 months of age^[161].