Changes in cholesterol homeostasis associated with aging and with age-related conditions: pathophysiological and clinical implications

The increase in life expectancy is leading to a progressive rise in the percentage of older people in the general population, and consequently in the prevalence of chronic diseases, often leading to disability. Age-related modifications in cholesterol homeostasis, the increase in plasma cholesterol levels due to aging, represents a cardio- and cerebrovascular risk factor in adjunct to age itself. Direct knowledge about the pathophysiological alterations of cholesterol metabolism is limited. Clinical-experimental evidence about cholesterol lowering treatment suggests that the benefits observed in the general population are also observed in older age groups. However, patients enrolled in clinical trials often do not represent real-life clinical scenarios, limiting the generalizability of research findings. Issues of complexity and frailty are mostly inadequately addressed in published studies and guidelines. Further, effects of cholesterol itself and cholesterol lowering on cognitive function are still controversial. This narrative review focuses on current evidence about the pathophysiology and clinical implications of the relationship between cholesterol and aging. Some suggestions will be provided, underlining the need for careful, personalized evaluation of the patient's functional status, along with clinical competence and geriatric skills.