One important component of aging is an inability of the body to break down some metabolic waste products that accumulate slowly over life. Small amounts are largely harmless, but by old age these accumulations become large enough and prevalent enough to cause disease. Atherosclerosis, for example, is associated with the buildup of oxidized cholesterols known as oxysterols, such as 7-ketocholesterol.
The SENS approach to removing this contribution to aging is medical bioremediation: find enzymes in wild bacteria species that can be adapted for use in human tissues to safely break down the problem waste products. Research has been ongoing at a low level of funding for a few years now, with 7-ketocholesterol as one of the early targets.
Here, researchers examine in more detail just how 7-ketocholesterol causes harm:
The damage of barrier tissues, such as the vascular endothelium and intestinal epithelium, may lead to disturbances of local immune homeostasis. The aim of the study was to assess and compare the effect of oxidized cholesterols (7-ketocholesterol and 25-hydroxycholesterol) on the barrier properties of human primary aortic endothelium (HAEC) and intestinal epithelium cells.
7-ketocholesterol [caused] extensive damage to the endothelial monolayer, while 25-hydroxycholesterol caused partial damage and did not affect the epithelial monolayer. 7-ketocholesterol, but not 25-hydroxycholesterol, increased endothelial cell apoptosis and decreased the viability of endothelial cells.
Oxidized cholesterols destroy the HAEC, but not the epithelial barrier, via cell apoptosis dependent on the site of oxidation. Damage to the endothelium by oxidized cholesterol may disrupt local homeostasis and provide open access to inner parts of the vascular wall for lipids, other peripheral blood-derived agents, and immune cells, leading to inflammation and atherogenesis.