Modulatory influences on ageing of the vasculature in healthy humans

doi:10.1016/j.exger.2006.01.001

Experimental Gerontology

Volume 41, Issue 5, May 2006, Pages 501-507

https://doi.org/10.1016/j.exger.2006.01.001 Get rights and content

Abstract

Increased arterial stiffness and impaired vascular endothelial function are the two most clinically important events that occur with vascular ageing in humans. Together they contribute to age-associated increases in systolic hypertension, left ventricular remodeling and diastolic dysfunction, coronary artery and other atherosclerotic vascular diseases, congestive heart failure, and the attendant cardiac events such as myocardial infarction. However, there is marked individual variability in arterial stiffness and endothelial function with advancing age, which suggests modulation by one or, more likely, several biological and/or lifestyle factors. Consistent with this idea, habitual aerobic exercise appears to attenuate or completely prevent these adverse changes. Other factors including sex hormone status, circulating total and low-density lipoprotein-cholesterol levels, total body and abdominal fatness, and dietary sodium intake also appear to influence arterial stiffening and endothelial dysfunction with ageing. It is now clear that a number of physiological factors and lifestyle behaviors collectively determine how much and, perhaps in some cases, if functionally or clinically significant vascular ageing occurs in adult humans. Of these, the existing evidence indicates that habitual aerobic exercise may be the single most important modulatory influence.

Section snippets

Increased arterial stiffness

One key vascular change with ageing is an increase in arterial stiffness. In humans, this typically is demonstrated by increases in systolic augmentation of the arterial pressure wave (i.e. increased augmentation index), increased aortic pulse wave velocity (PWV), and/or reductions in ultrasound-determined large elastic artery compliance (Avolio et al., 1985, Vaitkevicius et al., 1993, Rajkumar et al., 1997, Sutton-Tyrrell et al., 2001, Gates et al., 2004). This single vascular alteration

Vascular endothelial dysfunction

The second major change with vascular ageing is a reduction in endothelial function, most often shown as impaired endothelium-dependent dilation (EDD) of peripheral resistance vessels and conduit arteries (Celermajer et al., 1994, Taddei et al., 1995). In peripheral resistance vessels, EDD is conventionally determined by the increase in whole-forearm blood flow in response to intra-brachial artery infusion of an endothelium-dependent dilator such as acetylcholine, whereas EDD of peripheral

Modulatory influences on vascular ageing

Arterial stiffening and EDD vary widely even among healthy middle-aged and older adults (DeSouza et al., 2000, Tanaka et al., 2000, Moreau et al., 2003, Eskurza et al., 2004). This observation suggests that one or, most likely, several factors influence these vascular properties with adult ageing. Below we provide a brief summary of some of the factors that either have been established or are emerging as possible modulators of arterial stiffening and EDD with ageing in humans.

Conclusions

In conclusion, vascular ageing is now understood to be a key therapeutic target in the prevention of CVD (Najjar et al., 2005). Age-associated increases in arterial stiffness and reductions in EDD are the two most clinically significant events associated with vascular ageing in humans. A number of physiological factors and lifestyle behaviors affect the time course and magnitude of these events with ageing, including habitual aerobic exercise, HRT, plasma lipids and lipoproteins, total and

Acknowledgements

We acknowledge the work of previous principal investigators on the research cited from our laboratory, particularly that of Drs Christopher DeSouza and Hirofumi Tanaka. Our research was supported by NIH National Institute on Aging awards AG006537, AG013038, AG022241, AG020683, NIH NCRR General Clinical Research Center grant 5-01-RR00051, and American Heart Association fellowship award 02625451Z.

References (40)

D.S. Celermajer et al.
Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women
J. Am. Coll. Cardiol.
(1994)
R.H. Mackey et al.
Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study
Am. J. Hypertens.
(2002)
A. Miyoshi et al.
Impairment of endothelial function in salt-sensitive hypertension in humans
Am. J. Hypertens.
(1997)
T. Neunteufl et al.
Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain
Am. J. Cardiol.
(2000)
C.J. Rodriguez et al.
Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus
Am. J. Cardiol.
(2005)
D.R. Seals et al.
Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness
J. Am. Coll. Cardiol.
(2001)
H. Tanaka et al.
Hemodynamic sequelae of age-related increases in arterial stiffness in healthy women
Am. J. Cardiol.
(1998)
Almasi, S.J., Kahn, Z.D., Seals, D.R., & Eskurza I., 2005. “Normal” levels of LDL-cholesterol modulate...
A.P. Avolio et al.
Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China
Circulation
(1985)
P.J. Best et al.
The effect of estrogen replacement therapy on plasma nitric oxide and endothelin-1 levels in postmenopausal women
Ann. Intern. Med.
(1998)

E. Bragulat et al.

Endothelial dysfunction in salt-sensitive essential hypertension

Hypertension

(2001)

C.A. DeSouza et al.

Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men

Circulation

(2000)

I. Eskurza et al.

Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing

J. Physiol.

(2004)

I. Eskurza et al.

Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults

J. Physiol.

(2005)

P.E. Gates et al.

Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension

Hypertension

(2004)

M. Gerhard et al.

Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women

Circulation

(1998)

Holloszy, J., Khort, W., 1995. Aging: exercise. In: Handbook of Physiology. Oxford University Press, New York, pp....

L.J. Joseph et al.

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men

Int. J. Obes. Relat. Metab. Disord.

(2002)

L. Lind et al.

A comparison of three different methods to evaluate endothelium-dependent vasodilation in the elderly: the prospective investigation of the vasculature in uppsala seniors (PIVUS) study

Arterioscler. Thromb. Vasc. Biol.

(2005)

M. Matsuda et al.

Effects of physical exercise on the elasticity and elastic components of the rat aorta

Eur. J. Appl. Physiol. Occup. Physiol.

(1993)

Cited by (70)

Heterogeneity of aging and mortality risk among individuals with hypertension: Insights from phenotypic age and phenotypic age acceleration
2024, Journal of Nutrition, Health and Aging
Hypertension, a key contributor to mortality, is impacted by biological aging. We investigated the relationship between novel biological aging metrics - Phenotypic Age (PA) and Phenotypic Age Acceleration (PAA) - and mortality in individuals with hypertension, exploring the mediating effects of arterial stiffness (estimated Pulse Wave Velocity, ePWV), and Heart/Vascular Age (HVA).
Using data from 62,160 National Health and Nutrition Examination Survey (NHANES) participants (1999–2010), we selected 4,228 individuals with hypertension and computed PA, PAA, HVA, and ePWV. Weighted, multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating PA, PAA to mortality, and mediation roles of ePWV, PAA, HVA were evaluated. Mendelian randomization (MR) analysis was employed to investigate causality between genetically inferred PAA and hypertension.
Over a 12-year median follow-up, PA and PAA were tied to increased mortality risks in individuals with hypertension. All-cause mortality hazard ratios per 10-year PA and PAA increments were 1.96 (95% CI, 1.81–2.11) and 1.67 (95% CI, 1.52–1.85), respectively. Cardiovascular mortality HRs were 2.32 (95% CI, 1.97–2.73) and 1.93 (95% CI, 1.65–2.26) for PA and PAA, respectively. ePWV, PAA, and HVA mediated 42%, 30.3%, and 6.9% of PA’s impact on mortality, respectively. Mendelian randomization highlighted a causal link between PAA genetics and hypertension (OR = 1.002; 95% CI, 1.000–1.003).
PA and PAA, enhancing cardiovascular risk scores by integrating diverse biomarkers, offer vital insights for aging and mortality evaluation in individuals with hypertension, suggesting avenues for intensified aging mitigation and cardiovascular issue prevention. Validations in varied populations and explorations of underlying mechanisms are warranted.
The physiologic benefits of optimizing cardiorespiratory fitness and physical activity – From the cell to systems level in a post-pandemic world
2024, Progress in Cardiovascular Diseases
Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.
Potential health effects of dietary nitrate supplementation in aging and chronic degenerative disease
2020, Medical Hypotheses
Citation Excerpt :
A healthy, phenotypic expression of the endothelial layer favors vasodilation through the release of nitric oxide (NO), which possesses a strong inhibitory effect on coagulation and platelet aggregation thereby improving flow and fluidity. However, aging is accompanied by functional and structural changes of the endothelium and surrounding vessel layers that make up the vascular wall [4]. Prior to a clinical diagnosis, early signs of vascular aging coincide with reduced NO bioavailability – a key feature attributed to diminishing endothelial-dependent vasodilation and arterial stiffening [5].
In the United States, latest projections indicate the number of adults 65 years of age and older is expected to double by 2050. Given that increased oxidative stress is a hallmark of aging, it is understandable that waning nitric oxide and chronic degenerative disease arise in tandem. To this end, translational evidence-based strategies are needed to mitigate the impending toll on personal and public health. Dietary nitrate supplementation, particularly in the form of beetroot juice, is an active area of inquiry that has gained considerable attention in recent years. Compelling evidence has revealed beetroot juice can elicit potent physiological responses that may offer associated health benefits for multiple clinical disorders including hypertension, dementia, and sarcopenia. Even in the absence of overt disease, age-related impairments in cardiovascular and skeletal muscle function may uniquely benefit from beetroot juice supplementation as evidence has shown blood pressure lowering effects and improved muscle function/contractility – presumably from increased nitric oxide bioavailability. This, in turn, presents a practical opportunity for susceptible populations to support ease of movement and exercise tolerance, both of which may promote free-living physical activity. A theoretical rationale details the potential health effects of dietary nitrate supplementation, wherein a working framework hypothesizes beetroot juice consumption prior to structured exercise training may offer synergistic benefits to aid healthy aging and independent-living among older adults.
Using Psyllium to Prevent and Treat Obesity Comorbidities
2014, Nutrition in the Prevention and Treatment of Abdominal Obesity
Current evidence supports the notion that the consumption of a high-fiber diet provides benefits to many components of metabolic syndrome (MS), cardiovascular disease, and type 2 diabetes. Psyllium is one of the most widely used fiber supplements because it is reasonably cheap and is better tolerated than other fiber supplements. Psyllium supplementation reduces appetite, improves blood glucose levels and the insulin response, reduces blood pressure, and has beneficial effects on the lipid profile in both animals and humans, thereby reducing metabolic risk factors. Psyllium seems to improve body weight in animals, but its effects on body weight in humans is unresolved. Psyllium supplementation may be beneficial for patients with metabolic syndrome risk factors such as hypercholesterolemia, hypertriglyceridemia, and hyperglycemia, but its efficacy in the management of body weight, body composition, appetite, and hypertension requires further investigation.
Estimated pulse wave velocity as a measure of vascular aging
2023, PLoS ONE
The Impact of Training on the Loss of Cardiorespiratory Fitness in Aging Masters Endurance Athletes
2022, International Journal of Environmental Research and Public Health

View all citing articles on Scopus

View full text

Modulatory influences on ageing of the vasculature in healthy humans

Abstract

Section snippets

Increased arterial stiffness

Vascular endothelial dysfunction

Modulatory influences on vascular ageing

Conclusions

Acknowledgements

J. Am. Coll. Cardiol.

Am. J. Hypertens.

Am. J. Hypertens.

Am. J. Cardiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China

Circulation

The effect of estrogen replacement therapy on plasma nitric oxide and endothelin-1 levels in postmenopausal women

Ann. Intern. Med.

Endothelial dysfunction in salt-sensitive essential hypertension

Hypertension

Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men

Circulation

Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing

J. Physiol.

Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults

J. Physiol.

Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension

Hypertension

Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women

Circulation

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men

Int. J. Obes. Relat. Metab. Disord.

A comparison of three different methods to evaluate endothelium-dependent vasodilation in the elderly: the prospective investigation of the vasculature in uppsala seniors (PIVUS) study

Arterioscler. Thromb. Vasc. Biol.

Effects of physical exercise on the elasticity and elastic components of the rat aorta

Eur. J. Appl. Physiol. Occup. Physiol.