Breaking News
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
February 15, 2019 - New DNA methylation GrimAge tool allows you to predict lifespan and healthspan
February 15, 2019 - New AI-driven platform analyze how pathogens infect human cells
February 15, 2019 - Increased activity of EHMT2 gene deficient neurons could cause autism in humans
February 15, 2019 - Recurring UTIs may mask symptoms of bladder or kidney cancer
February 15, 2019 - Researchers conduct extensive comparison of drugs used in treating neuroendocrine tumors
February 15, 2019 - Depression prevention for pregnant women and new mothers – new recommendations
February 15, 2019 - AHA News: Are There Health Benefits From Chocolate?
February 15, 2019 - The involvement of the gut in Parkinson’s disease: hype or hope?
February 15, 2019 - New PET imaging agent may help measure efficacy or failure of hormone therapy for breast cancer
February 15, 2019 - Preventing infections could help combat antimicrobial resistance
February 15, 2019 - Study investigates the role of estrogen in controlling glucose homeostasis
February 15, 2019 - Exposure to chemical in weedkiller Roundup raises risk of some cancers, study finds
February 15, 2019 - Smoking and drinking during pregnancy – stigma drives women to secrecy
February 15, 2019 - Low FODMAP diet reduces stomach issues caused by exercise
February 15, 2019 - Novel approach uses small amounts of tissue to quantify PD-L1 expression levels in tumors
February 15, 2019 - Breast pumps could be transmitting asthma-causing bacteria in babies, finds study
February 15, 2019 - The Pistoia Alliance Launches Next Phase of Blockchain Project to Develop Life Science R&D Use Cases
February 15, 2019 - The search for environmental causes of Parkinson’s disease moves forward
February 15, 2019 - Women scientists inhibited by funding methods that favor men, researchers say
February 14, 2019 - Few primary care physicians lack enough knowledge of cancer treatment options
February 14, 2019 - Prime real estate is determined by previous owner in the squirrel world
February 14, 2019 - Discovery of a ‘master switch’ within the immune system
February 14, 2019 - Health officers with surgical training are a safe alternative for performing C-sections
Boosting enzyme may help improve blood flow, fitness in elderly

Boosting enzyme may help improve blood flow, fitness in elderly

image_pdfDownload PDFimage_print
An enzyme called SIRT1 declines in the blood vessels with age and restoring it reverses the effects of vascular aging. After receiving a supplement called NMN, older mice showed increased capillary density, blood flow, mobility, and endurance. Credit: Cell; Zolt Arany, Perelman School of Medicine, University of Pennsylvania

As people age, their blood-vessel density and blood flow decrease, which is why it’s harder to maintain muscle mass after 40 and endurance in the later decades, even with exercise. This vascular decline is also one of the major causes of age-related diseases, such as frailty or hypertension. However, little is known about the underlying cause or how to stop it.

Now, in a new study published this week in Cell, a team of researchers from Penn Medicine and other institutions have shown for the first time how a well-studied enzyme called SIRT1 declines in the blood vessels with age and that restoring it reverses the effects of vascular aging. After receiving a supplement called NAD+ precursor nicotinamide mononucleotide (NMN), older mice had the number of capillaries and capillary density found in much younger mice, and improved endurance by up to 80 percent. The collaborative study also involves researchers from Harvard Medical School and Massachusetts Institute of Technology.

“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,” said co-senior author Zoltan Pierre Arany, MD, PhD, an associate professor of Cardiovascular Medicine in the Perelman School of Medicine at the University of Pennsylvania. “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.”

The preclinical results show for the first time the ability to improve vascular health by increasing SIRT1, but they also have important implications for the prevention of age-related diseases, including cardiovascular disease, and aging itself. Identifying a target such as an enzyme that could be restored in a person’s vessels is an important step that could lead to new or modified existing therapeutics to treat diseases or slow down aging.

SIRT1 is a member of a family of enzymes that mediate the health benefits of diet and can extend lifespan when overexpressed, researchers have shown in past studies. It’s known that in young muscle SIRT1 is required for developing new and stronger blood vessels and is implicated in the deterioration of cells that line vessels. It was, however, unknown whether SIRT1 regulates vascular health in skeletal muscle tissue, and if so, whether its breakdown with age was reversible.

To test if SIRT1 was required for vessel creation and maintenance, the researchers knocked out its gene in mice and found that the density and number of capillaries was significantly lower compared to untreated mice, who in a high intensity endurance test ran twice as long as the mice without SIRT1.

Now, knowing that SIRT1 was necessary for vascularization, the researchers administered the NMN supplement to 18-month-old mice for two months and compared their blood vessels to six-month-old mice. NMN restored the number of capillaries and capillary density of the old mice to those typically seen in young mice and also dramatically increased their oxygen consumption. The most striking effect was a 56 to 80 percent improvement in endurance during a high-intensity, treadmill exercise test. Combining hydrogen sulfide, another molecule known to increase SIRT1, with NMN also increased capillary density in mice as old as 32 months compared to younger mice.

To the authors’ knowledge, this is the first time small molecules have induced the formation of new blood vessels at an advanced age in an animal model.

Overall, the researchers show in mice that loss of SIRT1 resulted in an early decline in skeletal muscle vascular density and exercise capacity, while overexpression of SIRT1 in older mice had a protective effect, ostensibly by sensitizing these cells to vascular endothelial growth factor coming from muscle fibers, the authors said.

The next step, Arany said, is to look for evidence of this mechanism at play in humans and for a more robust pharmaceutical agent that would be appropriate and effective for use in the clinic. NMN supplements marketed as having anti-aging properties exist today, but very few, if any, have clinical evidence to back up that claim. Researchers also used a larger dosage in the study compared to what’s on the market.

“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.”


Explore further:
Insights into the molecular mechanisms leading to kidney dysfunction in diabetic patients

Journal reference:
Cell

Provided by:
Perelman School of Medicine at the University of Pennsylvania

Tagged with:

About author

Related Articles