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  1. Article ; Online: Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions.

    Freeberg, Kaitlin A / Udovich, CeAnn C / Martens, Christopher R / Seals, Douglas R / Craighead, Daniel H

    The journals of gerontology. Series A, Biological sciences and medical sciences

    2023  Volume 78, Issue 12, Page(s) 2435–2448

    Abstract: Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide ... ...

    Abstract Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide mononucleotide, has profound effects on physiological function in models of aging and disease. Translation of these compounds for oral supplementation in humans has been increasingly studied within the last 10 years; however, the clinical evidence that raising NAD+ concentrations can improve physiological function is unclear. The goal of this review was to synthesize the published literature on the effects of chronic oral supplementation with NAD+ precursors on healthy aging and age-related chronic diseases. We identified nicotinamide riboside, nicotinamide riboside co-administered with pterostilbene, and nicotinamide mononucleotide as the most common candidates in investigations of NAD+-boosting compounds for improving physiological function in humans. Studies have been performed in generally healthy midlife and older adults, adults with cardiometabolic disease risk factors such as overweight and obesity, and numerous patient populations. Supplementation with these compounds is safe, tolerable, and can increase the abundance of NAD+ and related metabolites in multiple tissues. Dosing regimens and study durations vary greatly across interventions, and small sample sizes limit data interpretation of physiological outcomes. Limitations are identified and future research directions are suggested to further our understanding of the potential efficacy of NAD+-boosting compounds for improving physiological function and extending human health span.
    MeSH term(s) Humans ; Aged ; NAD/metabolism ; Nicotinamide Mononucleotide/metabolism ; Aging ; Obesity ; Dietary Supplements
    Chemical Substances NAD (0U46U6E8UK) ; Nicotinamide Mononucleotide (1094-61-7)
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glad106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: NAD

    Freeberg, Kaitlin A / Ludwig, Katelyn R / Chonchol, Michel / Seals, Douglas R / Rossman, Matthew J

    Nitric oxide : biology and chemistry

    2023  Volume 140-141, Page(s) 1–7

    Abstract: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), induces vascular endothelial dysfunction, but the mechanisms are unknown. We tested the hypothesis that the "circulating milieu" (plasma) of patients with COVID-19 would cause ... ...

    Abstract SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), induces vascular endothelial dysfunction, but the mechanisms are unknown. We tested the hypothesis that the "circulating milieu" (plasma) of patients with COVID-19 would cause endothelial cell dysfunction (characterized by lower nitric oxide (NO) production), which would be linked to greater reactive oxygen species (ROS) bioactivity and depletion of the critical metabolic co-substrate, nicotinamide adenine dinucleotide (NAD
    MeSH term(s) Male ; Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; NAD/metabolism ; NAD/pharmacology ; Reactive Oxygen Species/metabolism ; Nitric Oxide/metabolism ; Endothelial Cells/metabolism ; COVID-19 ; SARS-CoV-2 ; Oxidative Stress ; Nicotinamide Mononucleotide/metabolism ; Nicotinamide Mononucleotide/pharmacology
    Chemical Substances NAD (0U46U6E8UK) ; Reactive Oxygen Species ; Nitric Oxide (31C4KY9ESH) ; Nicotinamide Mononucleotide (1094-61-7)
    Language English
    Publishing date 2023-08-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1362794-6
    ISSN 1089-8611 ; 1089-8603
    ISSN (online) 1089-8611
    ISSN 1089-8603
    DOI 10.1016/j.niox.2023.08.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clinical assessments of cerebrovascular health: is there a neED(D) for cerebral shear-mediated dilatation?

    Coppock, McKinley E / Freeberg, Kaitlin A / Darvish, Sanna / Murray, Kevin O

    The Journal of physiology

    2022  Volume 600, Issue 6, Page(s) 1287–1289

    MeSH term(s) Dilatation ; Endothelium, Vascular ; Nitric Oxide ; Nitric Oxide Synthase Type III ; Stress, Mechanical ; Vasodilation
    Chemical Substances Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type III (EC 1.14.13.39)
    Language English
    Publishing date 2022-02-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP282766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Vascular Endothelial Function in Midlife/Older Adults Classified According to 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines.

    Craighead, Daniel H / Freeberg, Kaitlin A / Seals, Douglas R

    Journal of the American Heart Association

    2020  Volume 9, Issue 17, Page(s) e016625

    Abstract: Background Impaired endothelial function is thought to contribute to the increased cardiovascular risk associated with above-normal blood pressure (BP). However, the association between endothelial function and BP classified by 2017 American College of ... ...

    Abstract Background Impaired endothelial function is thought to contribute to the increased cardiovascular risk associated with above-normal blood pressure (BP). However, the association between endothelial function and BP classified by 2017 American College of Cardiology/American Heart Association guidelines is unknown. Our objective was to determine if endothelial function decreases in midlife/older adults across the 2017 American College of Cardiology/American Heart Association guidelines BP classifications and identify associated mechanisms of action. Methods and Results A retrospective analysis of endothelial function (brachial artery flow-mediated dilation) from 988 midlife/older adults (aged 50+ years) stratified by BP status (normal BP; elevated BP; stage 1 hypertension; stage 2 hypertension) was performed. Endothelium-independent dilation (sublingual nitroglycerin), reactive oxygen species-mediated suppression of endothelial function (∆brachial artery flow-mediated dilation with vitamin C infusion), and endothelial cell and plasma markers of oxidative stress and inflammation were assessed in subgroups. Compared with normal BP (n=411), brachial artery flow-mediated dilation was 12% (
    MeSH term(s) Aged ; American Heart Association ; Ascorbic Acid/administration & dosage ; Ascorbic Acid/pharmacology ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Brachial Artery/physiopathology ; Cardiology/organization & administration ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/physiopathology ; Case-Control Studies ; Cross-Sectional Studies ; Endothelial Cells/metabolism ; Endothelium, Vascular/physiopathology ; Female ; Guidelines as Topic ; Humans ; Hypertension/classification ; Hypertension/physiopathology ; Inflammation/metabolism ; Interleukin-6/blood ; Male ; Middle Aged ; NADPH Oxidases/metabolism ; Nitroglycerin/administration & dosage ; Nitroglycerin/pharmacology ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; Regional Blood Flow/drug effects ; Retrospective Studies ; United States/epidemiology ; Vasodilation/drug effects
    Chemical Substances Interleukin-6 ; Reactive Oxygen Species ; NADPH Oxidases (EC 1.6.3.-) ; Nitroglycerin (G59M7S0WS3) ; Ascorbic Acid (PQ6CK8PD0R)
    Language English
    Publishing date 2020-08-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.120.016625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Translational Potential of High-Resistance Inspiratory Muscle Strength Training.

    Craighead, Daniel H / Freeberg, Kaitlin A / Maurer, Grace S / Myers, Valerie H / Seals, Douglas R

    Exercise and sport sciences reviews

    2022  Volume 50, Issue 3, Page(s) 107–117

    Abstract: Age-associated cardiovascular (CV) dysfunction increases the risk for CV diseases. Aerobic exercise training can improve CV function, but only a minority of adults meet aerobic exercise guidelines. High-resistance inspiratory muscle strength training is ... ...

    Abstract Age-associated cardiovascular (CV) dysfunction increases the risk for CV diseases. Aerobic exercise training can improve CV function, but only a minority of adults meet aerobic exercise guidelines. High-resistance inspiratory muscle strength training is a time-efficient lifestyle intervention that may promote adherence and improve CV function. However, further investigation is needed to translate inspiratory muscle strength training into the public health domain.
    MeSH term(s) Adult ; Exercise/physiology ; Exercise Tolerance/physiology ; Humans ; Muscle Strength/physiology ; Muscles ; Resistance Training ; Respiratory Muscles/physiology
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 187040-3
    ISSN 1538-3008 ; 0091-6331
    ISSN (online) 1538-3008
    ISSN 0091-6331
    DOI 10.1249/JES.0000000000000293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults.

    Freeberg, Kaitlin A / Craighead, Daniel H / Martens, Christopher R / You, Zhiying / Chonchol, Michel / Seals, Douglas R

    Frontiers in cardiovascular medicine

    2022  Volume 9, Page(s) 881703

    Abstract: Background: Aging is the primary risk factor for cardiovascular diseases, the leading cause of death worldwide. Age-related increases in systolic blood pressure (SBP) link advancing age to cardiovascular disease risk. A key mechanism mediating the ... ...

    Abstract Background: Aging is the primary risk factor for cardiovascular diseases, the leading cause of death worldwide. Age-related increases in systolic blood pressure (SBP) link advancing age to cardiovascular disease risk. A key mechanism mediating the increase in SBP with aging is stiffening of the large elastic arteries, which occurs due to increases in oxidative stress, inflammation, and vascular smooth muscle tone. Nicotinamide adenine dinucleotide (NAD
    Methods: A randomized, double-blind, placebo-controlled, single-site parallel-group design clinical trial will be conducted in 94 (47/group) midlife and older (age ≥ 50 years) adults with initial above-normal SBP. Participants will complete baseline testing and then will be randomized to either nicotinamide riboside (500 mg, 2×/day, NIAGEN
    Discussion: This study is designed to establish the safety and efficacy of the NAD
    Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT03821623].
    Language English
    Publishing date 2022-05-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2022.881703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Time-efficient, high-resistance inspiratory muscle strength training for cardiovascular aging.

    Craighead, Daniel H / Freeberg, Kaitlin A / McCarty, Narissa P / Seals, Douglas R

    Experimental gerontology

    2021  Volume 154, Page(s) 111515

    Abstract: Cardiovascular diseases (CVD) remain the leading cause of death in developed and developing societies and aging is the primary risk factor for CVD. Much of the increased risk of CVD in midlife/older adults (i.e., adults aged 50 years and older) is due to ...

    Abstract Cardiovascular diseases (CVD) remain the leading cause of death in developed and developing societies and aging is the primary risk factor for CVD. Much of the increased risk of CVD in midlife/older adults (i.e., adults aged 50 years and older) is due to increases in blood pressure, vascular endothelial dysfunction and stiffening of the large elastic arteries. Aerobic exercise training is an effective lifestyle intervention to improve CV function and decrease CVD risk with aging. However, <40% of midlife/older adults meet guidelines for aerobic exercise, due to time availability-related barriers and other obstacles to adherence. Therefore, there is a need for new lifestyle interventions that not only improve CV function with aging but also promote adherence. High-resistance inspiratory muscle strength training (IMST) is an emerging, time-efficient (5 min/day) lifestyle intervention. Early research suggests high-resistance IMST may promote adherence, lower blood pressure and potentially improve vascular endothelial function. However, additional investigation will be required to more definitively establish high-resistance IMST as a healthy lifestyle intervention for CV aging. This review will summarize the current evidence on high-resistance IMST for improving CV function with aging and will identify key research gaps and future directions.
    MeSH term(s) Aged ; Aging ; Arteries ; Blood Pressure ; Humans ; Middle Aged ; Muscle Strength ; Muscles ; Resistance Training
    Language English
    Publishing date 2021-08-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2021.111515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with "standard of care" aerobic exercise.

    Craighead, Daniel H / Freeberg, Kaitlin A / McCarty, Narissa P / Rossman, Matthew J / Moreau, Kerrie L / You, Zhiying / Chonchol, Michel / Seals, Douglas R

    Frontiers in physiology

    2022  Volume 13, Page(s) 967478

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-08-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.967478
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Overcoming exercise barriers: home-based HIT for reducing cardiovascular disease risk in obese individuals.

    McCarty, Narissa P / Craighead, Daniel H / Freeberg, Kaitlin A

    The Journal of physiology

    2019  Volume 598, Issue 1, Page(s) 13–14

    MeSH term(s) Cardiovascular Diseases ; Exercise ; Humans ; NAD ; Obesity
    Chemical Substances NAD (0U46U6E8UK)
    Language English
    Publishing date 2019-12-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP279074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Time-efficient, high-resistance inspiratory muscle strength training increases cerebrovascular reactivity in midlife and older adults.

    Freeberg, Kaitlin A / Craighead, Daniel H / Heinbockel, Thomas C / Rossman, Matthew J / Jackman, Rachel A / Jankowski, Lindsey R / Ludwig, Katelyn R / Chonchol, Michel / Bailey, E Fiona / Seals, Douglas R

    American journal of physiology. Heart and circulatory physiology

    2023  Volume 325, Issue 5, Page(s) H1059–H1068

    Abstract: Aging is associated with increased risk for cognitive decline and dementia due in part to increases in systolic blood pressure (SBP) and cerebrovascular dysfunction. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, ... ...

    Abstract Aging is associated with increased risk for cognitive decline and dementia due in part to increases in systolic blood pressure (SBP) and cerebrovascular dysfunction. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, intensive respiratory training protocol (30 resisted inspirations/day) that lowers SBP and improves peripheral vascular function in midlife/older adults with above-normal SBP. However, whether, and by what mechanisms, IMST can improve cerebrovascular function is unknown. We hypothesized that IMST would increase cerebrovascular reactivity to hypercapnia (CVR to CO
    MeSH term(s) Male ; Female ; Humans ; Aged ; Middle Aged ; Carbon Dioxide ; Acetylcholine ; Resistance Training ; Endothelial Cells ; Respiratory Muscles/physiology ; Dementia ; Muscle Strength/physiology
    Chemical Substances Carbon Dioxide (142M471B3J) ; Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00351.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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