Advanced Glycation End-Products Accelerate Cardiac Aging
Advanced glycation end-products (AGEs) of various forms are present in the diet, but also generated by our biochemistry as a form of metabolic waste. Some are short-lived and easily cleared by the body, but others are very persistent and form long-lasting cross-links that degrade tissue structure. Their growing presence is one of the contributing causes of degenerative aging, causing a range of effects such as inflammation, stiffening of blood vessels, loss of elasticity in skin, and loss of cartilage and bone strength.
Surprisingly, given how well this cause of aging is understood, there is comparatively little work on the development of therapies to clear the most prevalent AGEs, such as glucosepane in human tissues. Spurring progress in this field is one of the goals of the SENS Research Foundation, and the staff there coordinate early-stage research in a few laboratories, aiming to build the fundamental tools and methodologies needed to encourage a broader participation. The research linked below is one of many examples to demonstrate why we need AGE clearance as a part of any near-future rejuvenation toolkit, here focusing on the role of AGEs in encouraging cellular senescence and fibrosis:
The current study was carried out to evaluate the effect of advanced glycation end-products (AGE) on cardiac aging and to explore its underlying mechanisms. Neonatal rat cardiac fibroblasts were cultured and divided into four groups: control; AGE; AGE + receptor for AGE antibody and AGE + SB431542 (transforming growth factor-β [TGF-β]/Smad signaling pathway inhibitor, 10 μmol/L) group. After being cultured for 48 h, the cells were harvested and the senescence-associated beta-galactosidase expression was analyzed. Then the level of p16, TGF-β, Smad/p-smad and matrix metalloproteinase-2 was evaluated by western blot.Significantly increased senescence-associated beta-galactosidase activity as well as p16 level was observed in the AGE group. Furthermore, AGE also significantly increased the TGF-β1, p-smad2/3 and metalloproteinases-2 expression in cardiac fibroblasts. Meanwhile, either pretreatment with receptor for AGE antibody or SB431542 significantly inhibited the upregulated cardiac senescence (beta-galactosidase activity and P16) and fibrosis-associated (TGF-β1, p-smad2/3 and metalloproteinases-2) markers induced by AGE. Taken together, all these results suggested that AGE are an important factor for cardiac aging and fibrosis, whereas the receptor for AGE and TGF-β/Smad signaling pathway might be involved in the AGE-induced cardiac aging process.