7-Ketocholesterol and disease
7-Ketocholesterol, a toxic byproduct of oxidized cholesterol, is highly toxic and has no redeeming qualities. It serves no purpose within our bodies other than to allow heart disease. Learn more by reading the recent Underdog Pharma review on Science Direct!
Oxidative Stress has been implicated as a cause of aging for a long time [219-220]. As explained in section 2, the 7KC product is the most stable of a reaction between a cholesterol and a radical. It is a vicious circle, as 7KC leads to an increase in free radical release and production by permeabilizing the plasma membrane. As mentioned above, free radical formation and mitochondrial dysfunction are both strongly linked to the aging process.
Is 7KC an age-related biomarker? 7KC accumulation, as discussed in section 4, is directly linked to many aging diseases, such as atherosclerosis and heart failure. When diseases of aging that are otherwise unrelated share a cause, it is reasonable to assume that the cause is likely a biological process. 7KC accumulates in phagocytic cell types such as macrophages, RPE cells and microglia (which promote the formation of foam-like cells). It was also suggested that c.elegans exposed to 7KC might be a good example of 7KC-dependent ageing . It is possible that 7KC bioaccumulates with age as it is toxic and many cells have a difficult time metabolizing it.
7KC, as described in Section 3, is a powerful inhibitor of lysosomal functions. Lysosomal dysfunction is a part of degenerative aging and is implicated as causing diseases like AMD, atherosclerosis and AD, where accumulation of nondegradable biomolecules within the lysosomes prevents phagocytic cell from efficiently metabolizing biological material phagocytized . We propose, therefore, that 7KC plays a significant role in the loss associated with aging. The lysosomal dysfunction produced by 7KC may be a key mediator. As argued in previous sections, while diseases of aging can present with a variety of symptoms, the production and accumulation 7KC could be a key element for many of these symptoms. Although the biological effects 7KC has been studied at least since the 1940s there is little published data on the intracellular levels of 7KC with age.