Enzyme May Reverse Effects Of Vascular Aging

Researchers from Penn Medicine in collaboration with Massachusetts Institute of Technology and Harvard Medical School have shown that SIRT1 enzyme declines in blood vessels with age and restoring it reverses effects of vascular aging. After receiving NAD + precursor nicotinamide mononucleotide supplements older model mice were found to have had numbers of capillaries and capillary density found in younger mice and improved endurance of up to 80%.

Loss of SIRT1 is a primary reason why ability to exercise and gain benefits from it diminish with age. Bringing back the enzyme into blood vessels improves vascular health dramatically, old blood vessel trees in older mice turned into the equivalent of a young vessel tree that appeared as if it had been exercising for a while, according to the researchers as published in Cell.

Preclinical findings show ability to improve vascular health by increasing SIRT1 which has important implications for prevention of age related diseases including CVD and even aging itself. Identifying targets such as enzymes that may restore blood vessels could lead to new methods to treat disease and slow down aging.

SIRT1 enzymes help mediate benefits of diet and extend lifespan when overexpressed. SIRT1 from young muscle is required for developing new stronger blood vessels and is implicated in deterioration of cells lining vessels, whether it regulates vascular health in skeletal muscle tissue or if  age related breakdown was reversible is unknown.

Investigations whether SIRT1 was required for vessel maintenance and creation using knockout model mice revealed density and number of capillaries was much lower than that of untreated mice which ran twice as slow in high intensity endurance tests. During further investigations administering NMN supplement to 18 month old mice over 2 months restored number and capillary density of the older mice to that typical seen in younger mice, and increased oxygen consumption. A 56-80% improvement in endurance was observed in high intensity treadmill exercise testing. Combining NMN with hydrogen sulfide was also observed to increase capillary density in older mice.

Loss of SIRT1 resulted in early decline in skeletal muscle vascular density and exercise capability, overexpression in older mice had protective effects by sensitizing cells to vascular endothelial growth factor coming from muscle fibers, according to the researchers.

Next researchers will explore for evidence of the mechanism at play in humans for a more robust pharmaceutical agent appropriate for clinical use. NMN supplements with anti-aging properties exists and are currently marketed but few have clinical evidence as back up.