. 2019 May 1;30(3):177–185. doi: 10.1097/MOL.0000000000000602

Table 1.

Clarification of the mouse models used to study the relationship between senescence and cardiometabolic diseases

Mouse model	Description	Major findings	References
BubR1 hypomorphic mouse (BubR1^H/H)	BubR1 is a core protein of the spindle assembly checkpoint, a safeguard that ensures correct chromosome segregation. BubR1 hypomorphic mice produce 10% of the BubR1 protein.	BubR1^H/H is a model of accelerated ageing, as mice show markedly shortened lifespan and display several age-related diseases, including sarcopenia, cataracts, fat loss, arterial wall stiffening and impaired wound healing. BubR1^H/H mice accumulate p16^Ink4a-positive cells in several tissues, including adipose tissue, skeletal muscle and eye.	[30,31]
INK-ATTAC naturally aged mouse	The INK-ATTAC transgene allows for selective elimination of p16^Ink4a-positive cells upon administration of the synthetic drug AP20187, which induces dimerization of a membrane-bound myristoylated FK506-binding-protein-caspase 8 (FKBP-Casp8) fusion protein expressed specifically in senescent cells via the p16^Ink4a promoter. Furthermore, an internal ribosome entry site (IRES) followed by an open reading frame (ORF) coding for enhanced green fluorescence protein (EGFP), which allows detection and collection of p16^Ink4a-positive senescent cells is incorporated in the construct.	Clearance of p16^Ink4a-positive cells resulted in increased lifespan in male and female mice, delayed tumorigenesis and attenuated age-related diseases, including lipodystrophy, kidney dysfunction and cardiac dysfunction. Mechanistically, elimination of p16^Ink4a-positive cells enhanced adipogenic transcription factors, reduced circulating levels of activin A and reduced fat accumulation in the liver of aged mice.	[8,32,33^▪▪]
INK-ATTAC BubR1^H/H mouse	Incorporation of the INK-ATTAC transgene in the progeroid BubR1^H/H mouse.	Removal of p16^Ink4a-positive cells in a model of accelerated ageing resulted in delayed onset of age-associated features, including sarcopenia, cataracts and lipodystrophy.	[30]