Vascular Aging is Reversible

 NG Groups, 03.2018

Dietary supplement reversed vascular aging in mice, study says

March 23 (UPI) --  A supplement containing an enzyme helped reverse the effects of vascular aging in mice, offering hope for humans, according to new research.

Biologists at Penn Medicine, Harvard Medical School and Massachusetts Institute of Technology showed that lowered levels of SIRT1 decrease blood-vessel density and blood flow and that adding the molecule can reverse the effects of vascular aging. The findings were published Thursday in the journal Cell.

ARTICLE

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacetylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD + booster nicotinamide mononucleotide (NMN) improves blood flow  and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H 2 S), a DR mimetic and regulator of endothelial NAD + levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

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• "This study tells us that the loss of SIRT1 is a primary reason why our ability to exercise and receive its benefits diminish as we age," Dr. Zoltan Pierre Arany, an associate professor of Cardiovascular Medicine in the Perelman School of Medicine at Penn, said in a press release. "We also show that when we bring the enzyme back into the blood vessels, vascular health improves dramatically. The old blood vessel tree [cluster of capillaries] in the older mice is turned into a young vessel tree, one that looks like it's been exercising for a while, just by turning on this enzyme.
  That's the most powerful aspect of the study."  

  

  Researchers examined 20-month-old mice, which are comparable to 70-year-old people, giving them a supplement called NAD+ precursor nicotinamide mononucleotide for two months.

  At the end of the trial, the mice had the number of capillaries and capillary density found in much younger mice, their endurance increased by up to 80 percent and their oxygen consumption went up.

  They also found that combining hydrogen sulfide, another molecule known to increase SIRT1, with NMN, finding increased capillary density in mice as old as 32 months.

  It's known that in young muscle, SIRT1 is required for developing new and stronger blood vessels and is involved in the deterioration of cells that line vessels. In past studies, researchers have also shown that SIRT1 is a member of a family of enzymes that mediate the health benefits of diet and can extend lifespan.

  What wasn't known was whether SIRT1 regulates vascular health in skeletal muscle tissue and whether its breakdown with age was reversible.

  "We know that enzymes that regulate the fundamental metabolic program can go awry with age," Arany said. "And we now know that turning that around and fixing it improves the health of aging blood vessels, sufficiently enough so that we can see differences in performance such as exercise capacity. We are still a long way away from testing in humans, but this gives us direction, a target to work with."

  The researchers said their technique could lead to new or modified existing therapeutics to treat diseases, including cardiovascular conditions and aging itself.

  The results were met with optimism and skepticism.

  "I think it's quite an important paper," Dr. Eric Verdin, of the California-based Buck Institute for Research on Aging, who was not involved in the new research, told STAT. "It's probably not the magic pill everyone is looking for, but it's one more brick in our efforts to understand aging and healthspan." Email a colleague a link to the following article(s): CELL -ARTICLESwitch to Standard View Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging

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