Table 2.

The classification and research findings of genetically engineered mouse models of sarcopenia

Genetically engineered models	Strain	Mouse age a	Key findings	References
Gene knockout	IL‐10(−/−)	23 m	Energetic abnormalities may contribute metabolism to skeletal muscle weakness in this geriatric syndrome.	75
	IL‐10(−/−)	22–24 m	Ageing in IL‐10(−/−) is associated with reduced skeletal muscle mitochondrial death signalling and altered formation of autophagosomes.	76
	Sod1(−/−)	4–10 m	ROS‐associated motor nerve terminal dysfunction is a contributor to the observed muscle changes in Sod1(−/−) mice.	77
	Sod1(−/−)	1–9 m	Mitochondrial hydroperoxide generation is elevated prior to muscle atrophy.	78
	Sod1(−/−)	18–22 m	Sod1(−/−) mice display characteristics of normal ageing muscle in an accelerated manner.	79
	Sod1(−/−)	8–11 m	Studies have confirmed the feasibility of using in vivo redox status assessment in the progression of pathological processes such as sarcopenia.	80
	Sod1(−/−)	18–24 m	Reduced expression of the superoxide scavenger CuZnSOD in neuronal tissue can lead to later disruption of the neuromuscular junction and muscle atrophy and weakness in aged mice.	81
	Asnsd1(−/−)	8–11 m	Asnsd1(−/−) mice demonstrated severe muscle weakness.	82
	MIP(−/−)	4–20 m	Studies suggest a putative role for MIP in the decline of muscle function during ageing.	83
	HtrA2mnd2(−/−)	5–8 m	Loss of HtrA2/Omi protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia.	84
	NLRP3(−/−)	3, 12, 24 m	Studies have confirmed the NLRP3 inflammasome implication in muscular ageing and sarcopenia onset and progression.	85
Gene overexpression	TNF‐Tg	10 m	Studies suggest that pharmacologic inhibition of TRAF6 signalling in skeletal muscles during ageing could treat/prevent age‐related and RA‐related sarcopenia by preventing TNFα‐induced proteolysis and inhibiting of muscle fibre regeneration.	86
	(P)RR‐Tg	25 m	The present study demonstrates the use of (P)RR‐Tg mice as novel sarcopenia models.	87
mtDNA mutations	MCKPGC‐1αMut	10 m	The results suggest that increased muscle PGC‐1α expression is able to improve some premature ageing phenotypes in mutant mice without reversing the accumulation of mtDNA mutations.	88
	D257A	11,13 m	These findings demonstrate that mutations in mtDNA can be causal in sarcopenia by affecting the assembly of functional ETC complexes.	89
	D257A	8–15 m	Muscles from mtDNA mutant mice have been found to exhibit higher levels of mitochondrial fission and autophagy, which may contribute to the sarcopenic phenotype observed in premature ageing.	90

ETC, electron transport chain; PGC‐1α, peroxisome proliferator‐activated receptor γ coactivator‐1α; ROS, reactive oxygen species; TRAF6, TNF receptor‐associated factor 6.

^am, months.