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After ischemia, the supply of glucose and oxygen is blocked, the disturbance of tricarboxylic acid cycle and the production of ATP are significantly reduced, and the activity and energy supply of ionic pumps such as sodium-potassium pumps on the surface of the cell membrane (Na + − k + -ATPase) as well as Ca 2+ pumps in the inner mitochondrial membrane are consequently impaired, which results in a large amount of Na + influx, while a dysfunction of endoplasmic reticulum calcium pumps affects Ca 2+ reuptake, the Na + /Ca 2+ influx caused by mitochondrial dysfunction triggers cellular oedema and swelling at this stage (Wu et al., 2018)

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In the SCN and peripheral oscillators, aging was found to impair intracellular coupling and attenuate circadian output [69]