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They are likely systemic metabolic regulators rather than direct diabetogenic signals for aging, and most are interpretable as responses to aging physiology Thus, although collectively they may lower metabolic flexibility and ultimately produce dysglycaemia, no evidence suggests that any of these alone produce, or could produce, a lean elderly diabetic phenotype Thus, hormones may also then be categorized as secondary amplifiers within the hierarchy of SAGE-DM, in the context of cellular senescence, beta-cell senescence, and immune dysregulation Menopause Menopause is defined as 12 months of amenorrhoea due to ovarian follicle loss and is followed by higher rates of cardiovascular disease, bone loss, and cognitive decline