Abstract

Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.

Highlights

  • As the population ages, there is increased susceptibility to the onset of disease and age-related degenerative conditions, making aging a central area of interest in medical sciences research (Wagster et al 2012; Flowers et al 2016)

  • Aging involves multiple complex physiological changes that lead to increased inflammation and loss of homeostasis and resilience and impaired regenerative capacity

  • The role of inflammation in aging has been widely researched and the term “inflammaging” has been coined to summarize how the inflammatory milieu leads to degeneration (Minciullo et al 2016)

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Summary

Introduction

There is increased susceptibility to the onset of disease and age-related degenerative conditions, making aging a central area of interest in medical sciences research (Wagster et al 2012; Flowers et al 2016). Exposure to blood from young mice had a positive effect on stem cell proliferation in old mice, demonstrating how the systemic milieu can impact stem cell proliferation (Conboy et al 2005; Villeda et al 2011). Young animals injected with plasma from old mice displayed significantly less freezing behavior in the contextual fear conditioning paradigm and made a greater number of errors in the radial arm water maze paradigm, suggesting impaired learning and memory following intravenous injection with old plasma. These studies further highlight how the aged systemic milieu can impact the CNS by exerting a dampening effect on hippocampal neurogenesis. In addition to these in vivo studies, the negative impact of the aged systemic milieu on stem cell proliferation has been reproduced in vitro with various types of stem cells derived from mice or rats being cultured with serum

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