Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

Kaplon, Rachelle E.; Hill, Sierra D.; Bispham, Nina Z.; Santos-Parker, Jessica R.; Nowlan, Molly J.; Snyder, Laura L.; Chonchol, Michel; LaRocca, Thomas J.; McQueen, Matthew J.; Seals, Douglas R.

doi:10.18632/aging.100962

Cited by 55 publications

(47 citation statements)

References 96 publications

(120 reference statements)

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“…Still, this evidence suggests that translational studies of autophagy-enhancing nutraceuticals are warranted. Thus far, clinical trials are limited, but recent evidence demonstrates that trehalose supplementation in middle-aged/older adults does improve endothelial function, although the role of autophagy is not entirely clear (Kaplon et al, 2016). Nevertheless, these observations provide an experimental basis for future studies aimed at determining the effects autophagy-boosting compounds on arterial aging in humans.…”

Section: Nutritional Factors and Interventionsmentioning

confidence: 99%

Nutrition and other lifestyle influences on arterial aging

LaRocca

Martens

Seals

2017

Ageing Research Reviews

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As our world’s population ages, cardiovascular diseases (CVD) will become an increasingly urgent public health problem. A key antecedent to clinical CVD and many other chronic disorders of aging is age-related arterial dysfunction, characterized by increased arterial stiffness and impaired arterial endothelial function. Accumulating evidence demonstrates that diet and nutrition may favorably modulate these arterial functions with aging, but many important questions remain. In this review, we will summarize the available information on dietary patterns and nutritional factors that have been studied for their potential to reduce arterial stiffness and improve endothelial function with age, with an emphasis on: 1) underlying physiological mechanisms, and 2) emerging areas of research on nutrition and arterial aging that may hold promise for preventing age-related CVD.

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Section: Nutritional Factors and Interventionsmentioning

confidence: 99%

Nutrition and other lifestyle influences on arterial aging

LaRocca

Martens

Seals

2017

Ageing Research Reviews

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“…Although mTOR inhibition has pleiotropic effects beyond inducing autophagy, it represents an important target in treating cardiometabolic disease (231). Second, the naturally occurring disaccharide trehalose potently induces autophagy in vivo and is effective in treating NAFLD (68, 232), endothelial dysfunction (145, 233), and diabetes (41, 68, 234). Because orally administered trehalose does not efficiently cross the intestinal epithelium (235) and may cause modest weight gain in humans due to its conversion to glucose (233), widespread use awaits means of improving its pharmacological properties or exploring the use of closely related compounds (236).…”

Section: Looking Forward: Outstanding Fundamental Questions In the Romentioning

confidence: 99%

“…Second, the naturally occurring disaccharide trehalose potently induces autophagy in vivo and is effective in treating NAFLD (68, 232), endothelial dysfunction (145, 233), and diabetes (41, 68, 234). Because orally administered trehalose does not efficiently cross the intestinal epithelium (235) and may cause modest weight gain in humans due to its conversion to glucose (233), widespread use awaits means of improving its pharmacological properties or exploring the use of closely related compounds (236). Third, the polyamine spermidine can stimulate autophagy by modulating protein acetylation (237) and has shown promise in treating endothelial dysfunction (144, 238) and atherosclerosis (239) through autophagy-related mechanisms.…”

Section: Looking Forward: Outstanding Fundamental Questions In the Romentioning

confidence: 99%

Target acquired: Selective autophagy in cardiometabolic disease

et al. 2017

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The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components including protein aggregates, mitochondria, peroxisomes, inflammasomes, and lipid droplets. A primary route through which this challenge is met is selective autophagy, the targeting of specific cellular cargo for autophagic compartmentalization and lysosomal degradation. In addition to its roles in degradation, selective autophagy is emerging as an integral component of inflammatory and metabolic signaling cascades. In this review, we focus on emerging evidence and key questions about the role of selective autophagy in the cell biology and pathophysiology of metabolic diseases such as obesity, diabetes, atherosclerosis, and steatohepatitis. Essential players in these processes are the selective autophagy receptors, defined broadly as adapter proteins that both recognize cargo and target it to the autophagosome. Additional domains within these receptors may allow integration of information about autophagic flux with critical regulators of cellular metabolism and inflammation. Details regarding the precise receptors involved, such as p62 and NBR1, and their predominant interacting partners are just beginning to be defined. Overall, we anticipate the continued study of selective autophagy will prove informative in understanding the pathogenesis of metabolic diseases and to provide previously unrecognized therapeutic targets.

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“…In this regard, initial translational insight in humans suggests that trehalose supplementation improves forearm microvascular NO bioavailability and endothelial function in older adults (Kaplon et al . ); however, it is unclear if this effect was mediated by activation of autophagy or some other mechanism.…”

Section: Practical Alternatives To Caloric Restrictionmentioning

confidence: 99%

“…Future studies are warranted in order to determine the efficacy of these and other autophagy enhancing compounds for improving vascular function with ageing in humans. In this regard, initial translational insight in humans suggests that trehalose supplementation improves forearm microvascular NO bioavailability and endothelial function in older adults (Kaplon et al 2016); however, it is unclear if this effect was mediated by activation of autophagy or some other mechanism.…”

Section: Figure 3 Pharmacological and Nutraceutical Strategies (Intementioning

confidence: 99%

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

Martens

Seals

2016

J Physiol

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Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well-known benefits of chronic CR, long-term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular 'energy- and nutrient-sensing' mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long-term CR.

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Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

Cited by 55 publications

References 96 publications

Nutrition and other lifestyle influences on arterial aging

Nutrition and other lifestyle influences on arterial aging

Target acquired: Selective autophagy in cardiometabolic disease

Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

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