Are Advanced Glycation End-Products Protective as Well as Harmful?
Some of the important processes in aging are known to be initially protective at lower levels and later harmful. Senescent cell accumulation is a good example, as it acts to suppress cancer incidence by permanently removing the most at risk cells from the cell cycle. Yet as senescent cells gather in numbers over the years their actions significantly degrade tissue and organ function.
In the paper quoted below researchers propose that the formation of advanced glycation end-products (AGEs) has a similar protective effect when it comes to cancer, and provide some other benefits besides. Yet their presence is definitely harmful in a number of ways when significant amounts of long-lived AGEs are present, causing chronic inflammation and degrading the mechanical properties of tissues such as skin and blood vessel walls by forming cross-links between structural proteins.
Fortunately in both of these cases periodic removal - of senescent cells or AGE cross-links - on a timescale of once every decade or so would allow us to have our cake and eat it. It would prevent pathological levels of these changes from emerging, as we know humans are quite capable of living for three decades without suffering serious consequences from aging, while still permitting lower and possibly protective levels to arise.
Non-enzymatic formation of advanced glycation endproducts (AGEs) is associated with degenerative diseases. Chronic accumulation of AGEs with age in tissues especially in the extracellular matrix is well known and at least in part responsible for e.g., collagen crosslinking, tissue stiffening and thus induction of high blood pressure or diastolic heart failure. Binding of soluble AGEs to the receptor for AGEs, RAGE, induces an inflammatory response whereas the soluble form of RAGE (sRAGE) can inhibit inflammatory tissue injury like arteriosclerosis in mouse models.However, there are a number of indications that AGEs have protective effects as well. AGEs may inhibit lung tumor growth, glyoxal induced AGE modification of human heart muscle can reduce an ischemia reperfusion injury and AGEs from nutrition can reduce ROS induced cell damage. In summary, this indicates that protein glycation behaves like a double-edged sword. It induces tissue aging and degenerative diseases on the one hand, on the other hand, may also have protective effects, indicating a hormetic response.