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This transition is due to sII opening and the distortion of intramolecular interactions causing the breaking of salt bridges and making the subsequent oxygen binding process less demanding (34, 35, 56)

However, the sample available at the 6-year follow-up was not entirely comparable to the one selected for the main analyses, as it included subjects with a substantially better health profile (indicative of survival bias) compared to those lost to follow-up

This may limit the degradation of biological components, such as proteins, DNA and lipids, crucial for membrane integrity, as indicated by markers such as 8-Hydroxy-2-deoxyguanosine (8-OHDG), AMPK activation, and modulation of several other key factors

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