Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects

Tamas Kiss, Cory B. Giles, Stefano Tarantini, Andriy Yabluchanskiy, Priya Balasubramanian, Tripti Gautam, Tamas Csipo, Ádám Nyúl-Tóth, Agnes Lipecz, Csaba Szabo, Eszter Farkas, Jonathan D. Wren, Anna Csiszar, Zoltan Ungvari

    Research output: Contribution to journalArticle

    Abstract

    Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by treatment with the NAD+ booster nicotinamide mononucleotide (NMN) exerts significant vasoprotective effects, improving endothelium-dependent vasodilation, attenuating oxidative stress, and rescuing age-related changes in gene expression. Strong experimental evidence shows that dysregulation of microRNAs (miRNAs) has a role in vascular aging. The present study was designed to test the hypothesis that age-related NAD+ depletion is causally linked to dysregulation of vascular miRNA expression. A corollary hypothesis is that functional vascular rejuvenation in NMN-treated aged mice is also associated with restoration of a youthful vascular miRNA expression profile. To test these hypotheses, aged (24-month-old) mice were treated with NMN for 2 weeks and miRNA signatures in the aortas were compared to those in aortas obtained from untreated young and aged control mice. We found that protective effects of NMN treatment on vascular function are associated with anti-aging changes in the miRNA expression profile in the aged mouse aorta. The predicted regulatory effects of NMN-induced differentially expressed miRNAs in aged vessels include anti-atherogenic effects and epigenetic rejuvenation. Future studies will uncover the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments and determine the links between miRNAs regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging and major aging-related vascular diseases.

    Original languageEnglish (US)
    JournalGeroScience
    DOIs
    StateAccepted/In press - Jan 1 2019

    Fingerprint

    Nicotinamide Mononucleotide
    Rejuvenation
    MicroRNAs
    Epigenomics
    Aorta
    Blood Vessels
    NAD
    Gene Expression
    Gene Regulatory Networks
    Therapeutics
    Vascular Diseases
    Vasodilation
    Endothelium
    Oxidative Stress

    Keywords

    • Atherosclerosis
    • Endothelial dysfunction
    • Epigenetics
    • Oxidative stress
    • Senescence
    • Vascular aging
    • Vascular cognitive impairment

    ASJC Scopus subject areas

    • Aging
    • Geriatrics and Gerontology

    Cite this

    Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. / Kiss, Tamas; Giles, Cory B.; Tarantini, Stefano; Yabluchanskiy, Andriy; Balasubramanian, Priya; Gautam, Tripti; Csipo, Tamas; Nyúl-Tóth, Ádám; Lipecz, Agnes; Szabo, Csaba; Farkas, Eszter; Wren, Jonathan D.; Csiszar, Anna; Ungvari, Zoltan.

    In: GeroScience, 01.01.2019.

    Research output: Contribution to journalArticle

    Kiss, T, Giles, CB, Tarantini, S, Yabluchanskiy, A, Balasubramanian, P, Gautam, T, Csipo, T, Nyúl-Tóth, Á, Lipecz, A, Szabo, C, Farkas, E, Wren, JD, Csiszar, A & Ungvari, Z 2019, 'Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects', GeroScience. https://doi.org/10.1007/s11357-019-00095-x
    Kiss, Tamas ; Giles, Cory B. ; Tarantini, Stefano ; Yabluchanskiy, Andriy ; Balasubramanian, Priya ; Gautam, Tripti ; Csipo, Tamas ; Nyúl-Tóth, Ádám ; Lipecz, Agnes ; Szabo, Csaba ; Farkas, Eszter ; Wren, Jonathan D. ; Csiszar, Anna ; Ungvari, Zoltan. / Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. In: GeroScience. 2019.
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    abstract = "Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by treatment with the NAD+ booster nicotinamide mononucleotide (NMN) exerts significant vasoprotective effects, improving endothelium-dependent vasodilation, attenuating oxidative stress, and rescuing age-related changes in gene expression. Strong experimental evidence shows that dysregulation of microRNAs (miRNAs) has a role in vascular aging. The present study was designed to test the hypothesis that age-related NAD+ depletion is causally linked to dysregulation of vascular miRNA expression. A corollary hypothesis is that functional vascular rejuvenation in NMN-treated aged mice is also associated with restoration of a youthful vascular miRNA expression profile. To test these hypotheses, aged (24-month-old) mice were treated with NMN for 2 weeks and miRNA signatures in the aortas were compared to those in aortas obtained from untreated young and aged control mice. We found that protective effects of NMN treatment on vascular function are associated with anti-aging changes in the miRNA expression profile in the aged mouse aorta. The predicted regulatory effects of NMN-induced differentially expressed miRNAs in aged vessels include anti-atherogenic effects and epigenetic rejuvenation. Future studies will uncover the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments and determine the links between miRNAs regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging and major aging-related vascular diseases.",
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    AU - Giles, Cory B.

    AU - Tarantini, Stefano

    AU - Yabluchanskiy, Andriy

    AU - Balasubramanian, Priya

    AU - Gautam, Tripti

    AU - Csipo, Tamas

    AU - Nyúl-Tóth, Ádám

    AU - Lipecz, Agnes

    AU - Szabo, Csaba

    AU - Farkas, Eszter

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    AU - Csiszar, Anna

    AU - Ungvari, Zoltan

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    N2 - Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by treatment with the NAD+ booster nicotinamide mononucleotide (NMN) exerts significant vasoprotective effects, improving endothelium-dependent vasodilation, attenuating oxidative stress, and rescuing age-related changes in gene expression. Strong experimental evidence shows that dysregulation of microRNAs (miRNAs) has a role in vascular aging. The present study was designed to test the hypothesis that age-related NAD+ depletion is causally linked to dysregulation of vascular miRNA expression. A corollary hypothesis is that functional vascular rejuvenation in NMN-treated aged mice is also associated with restoration of a youthful vascular miRNA expression profile. To test these hypotheses, aged (24-month-old) mice were treated with NMN for 2 weeks and miRNA signatures in the aortas were compared to those in aortas obtained from untreated young and aged control mice. We found that protective effects of NMN treatment on vascular function are associated with anti-aging changes in the miRNA expression profile in the aged mouse aorta. The predicted regulatory effects of NMN-induced differentially expressed miRNAs in aged vessels include anti-atherogenic effects and epigenetic rejuvenation. Future studies will uncover the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments and determine the links between miRNAs regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging and major aging-related vascular diseases.

    AB - Understanding molecular mechanisms involved in vascular aging is essential to develop novel interventional strategies for treatment and prevention of age-related vascular pathologies. Recent studies provide critical evidence that vascular aging is characterized by NAD+ depletion. Importantly, in aged mice, restoration of cellular NAD+ levels by treatment with the NAD+ booster nicotinamide mononucleotide (NMN) exerts significant vasoprotective effects, improving endothelium-dependent vasodilation, attenuating oxidative stress, and rescuing age-related changes in gene expression. Strong experimental evidence shows that dysregulation of microRNAs (miRNAs) has a role in vascular aging. The present study was designed to test the hypothesis that age-related NAD+ depletion is causally linked to dysregulation of vascular miRNA expression. A corollary hypothesis is that functional vascular rejuvenation in NMN-treated aged mice is also associated with restoration of a youthful vascular miRNA expression profile. To test these hypotheses, aged (24-month-old) mice were treated with NMN for 2 weeks and miRNA signatures in the aortas were compared to those in aortas obtained from untreated young and aged control mice. We found that protective effects of NMN treatment on vascular function are associated with anti-aging changes in the miRNA expression profile in the aged mouse aorta. The predicted regulatory effects of NMN-induced differentially expressed miRNAs in aged vessels include anti-atherogenic effects and epigenetic rejuvenation. Future studies will uncover the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments and determine the links between miRNAs regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging and major aging-related vascular diseases.

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    KW - Vascular cognitive impairment

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