Abstract
Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.
Highlights
The root extract of Rhodiola rosea, known as the golden root, has been widely used in traditional and integrative medical practices in Europe and Asia, where it has been purported to mediate a variety of beneficial effects in humans, such as improved mood, improved physical and mental stamina, and enhanced protection against high altitude sickness [1]
We found that R. rosea extended lifespan independent of dietary yeast content in flies, the method by which dietary restriction (DR) is imposed in flies
We further examined the role that insulin-like growth factor signaling (IIS) might play in the action of R. rosea by examining the expression levels of the Drosophila insulin-like peptides
Summary
The root extract of Rhodiola rosea, known as the golden root, has been widely used in traditional and integrative medical practices in Europe and Asia, where it has been purported to mediate a variety of beneficial effects in humans, such as improved mood, improved physical and mental stamina, and enhanced protection against high altitude sickness [1]. The molecular action of R. rosea is not known, though its effects in worms suggest that it may act through hormesis [9], where pretreatment of a mildly toxic compound induces defense systems that further protect the organism against any additional stress [11]. DR, defined as a decreased total caloric intake in the absence of malnutrition, is considered the most robust non-genetic treatment for improving health and extending lifespan in model organisms This treatment has been shown to benefit most organisms tested, from yeast to primates [12,13,14,15], though a recent study has questioned its effectiveness in primates [16]. A plausible mode of action of R. rosea could be that it acts as a DR mimetic
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