Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice

Donato, Anthony J.; Walker, Ashley E.; Magerko, Katherine A.; Bramwell, R Colton; Black, Alex D.; Henson, Grant D.; Lawson, Brooke R.; Lesniewski, Lisa A.; Seals, Douglas R.

doi:10.1111/acel.12103

Cited by 153 publications

(202 citation statements)

References 67 publications

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“…2A), indicating excessive superoxide‐mediated endothelial dysfunction with aging. To further assess the influence of aging and NMN treatment on oxidative stress in arteries, aortas were used because of the greater amount of tissue provided for biochemical assay, as described previously (Sindler et al ., 2011; Donato et al ., 2013; LaRocca et al ., 2013; Gano et al ., 2014). Consistent with the results of the pharmacological‐function experiments with TEMPOL, compared with young mice, aortas from old animals exhibited increased superoxide production, directly assessed by electron paramagnetic resonance (EPR) spectroscopy (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously demonstrated that arterial SIRT1 activity is reduced with aging and contributes to the age‐related impairment in endothelial function (Donato et al ., 2011; Gano et al ., 2014). We and others also have shown that lifelong CR prevents (Csiszar et al ., 2009; Donato et al ., 2013) and short‐term CR reverses (Rippe et al ., 2010) the age‐associated decline in endothelial function and that these effects are associated with enhanced arterial SIRT1 activity. Consistent with these observations, we recently found that 4 weeks of treatment with the SIRT1 activator SRT1720 restores endothelial function (i.e., EDD) in old mice (Gano et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

“…These function‐based observations are supported by our direct assessments of arterial superoxide production using EPR spectroscopy, as well as our results for nitrotyrosine, a well‐established cellular marker of oxidative stress (Csiszar et al ., 2002; Sindler et al ., 2011; Fleenor et al ., 2012a; Donato et al ., 2013). Aging in control animals was associated with marked increases in both aortic superoxide production and nitrotyrosine abundance (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Aging in control animals was associated with marked increases in both aortic superoxide production and nitrotyrosine abundance (Fig. 2B,C), as we have reported previously (Rippe et al ., 2010; Sindler et al ., 2011; Fleenor et al ., 2012a, 2013; Donato et al ., 2013; LaRocca et al ., 2013). In response to NMN supplementation, we observed a normalization of aortic superoxide production and a marked reduction in nitrotyrosine abundance in old mice.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that lifelong caloric restriction (CR), as well as short‐term CR in old animals, prevents or reverses endothelial dysfunction and large elastic artery stiffening by reducing superoxide production, increasing NO bioavailability, and modifying structural proteins (Rippe et al ., 2010; Donato et al ., 2013). However, because adherence to CR is not practical for most humans, there is growing interest in pharmacological therapies that may induce the benefits of CR.…”

Section: Introductionmentioning

confidence: 99%

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Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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SummaryWe tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

et al. 2016

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To eat or not to eat – Anti‐ageing effects of energy restriction

Neves

Martins

Passos

et al. 2015

Anti‐ageing Nutrients

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Anthracycline chemotherapy‐mediated vascular dysfunction as a model of accelerated vascular aging

et al. 2021

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Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can "accelerate" these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents, and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in midlife (50-64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to agematched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induces a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps, and make recommendations for future research.

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Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice

Cited by 153 publications

References 67 publications

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

To eat or not to eat – Anti‐ageing effects of energy restriction

Anthracycline chemotherapy‐mediated vascular dysfunction as a model of accelerated vascular aging

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