The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly.

Bárbara S Rocha

doi:10.3389/fragi.2021.778467

Abstract

We are living longer. Are we living healthier? As we age, cellular and molecular damage reshape our physiological responses towards environmental and endogenous stimuli. The free radical theory of ageing has been proposed long before ageing has been considered a “scientific discipline” and, since then, has been discussed and upgraded as a major contributor to aberrant ageing. Assuming that ageing results merely from the accumulation of oxidative modifications of biomolecules is not only a simplistic and reductive view of such a complex and dynamic process, but also free radicals and related oxidants are now considered pivotal signalling molecules. The fine modulation of critical signalling pathways by redox compounds demands a novel approach to tackle the role of free radicals in ageing. Nitric oxide (⋅NO) is a paradigmatic example given its biological functions in cardiovascular, neurologic and immune systems. In addition to the canonical ⋅NO synthesis by a family of enzymes, nitrate from green leafy vegetables, is reduced to nitrite in the oral cavity which is further reduced to ⋅NO in the stomach. Boosting this nitrate-nitrite-NO pathway has been shown to improve gastrointestinal, cardiovascular, metabolic and cognitive performance both in humans and in animal models of disease. In the elderly, nitrate-derived ⋅NO has been shown improve several physiological functions that typically decline during ageing. In this paper, the role of nitrate and derived nitrogen oxides will be discussed while reviewing pre-clinical and clinical data on the cardiovascular, neuronal, musculoskeletal and metabolic effects of nitrate during healthy ageing.

Highlights

FROM THE FREE RADICAL THEORY OF AGEING TO THE NITRATE-NITRITE-NITRIC OXIDE PATHWAYAgeing and the physiological events that limit lifespan have been subject of intense research for many decades
Superoxide radical and hydrogen peroxide are two emerging examples of how oxidants may be produced by tightly controlled enzymatic reactions (Sies and Jones, 2020) and, nitric oxide (NO) is an additional example of a pleiotropic signalling radical with physiological relevance (Moncada and Higgs, 2006)
The pre-clinical and clinical data summarised suggest that diets rich in nitrate may prevent, reverse or mitigate the physiological decay observed during healthy ageing or ageassociated disorders

Summary

Introduction

FROM THE FREE RADICAL THEORY OF AGEING TO THE NITRATE-NITRITE-NITRIC OXIDE PATHWAYAgeing and the physiological events that limit lifespan have been subject of intense research for many decades. The role of nitrate and derived nitrogen oxides will be discussed while reviewing pre-clinical and clinical data on the cardiovascular, neuronal, musculoskeletal and metabolic effects of nitrate during healthy ageing. Increasing age is associated with physiological alterations in different organs, but is the major risk factor for the most prevalent diseases of the XXIst century including cardiovascular, oncological, neurodegenerative and metabolic disorders (Niccoli and Partridge, 2012).

Results

Conclusion