Abstract
Diversity is observed in the wave of global aging because it is a complex biological process exhibiting individual variability. To assess aging physiologically, markers for biological aging are required in addition to the calendar age. From a metabolic perspective, the aging hypothesis includes the mitochondrial hypothesis and the calorie restriction (CR) hypothesis. In experimental models, several compounds or metabolites exert similar lifespan-extending effects, like CR. However, little is known about whether these metabolic modulations are applicable to human longevity, as human aging is greatly affected by a variety of factors, including lifestyle, genetic or epigenetic factors, exposure to stress, diet, and social environment. A comprehensive analysis of the human blood metabolome captures complex changes with individual differences. Moreover, a non-targeted analysis of the whole blood metabolome discloses unexpected aspects of human biology. By using such approaches, markers for aging or aging-relevant conditions were identified. This information should prove valuable for future diagnosis or clinical interventions in diseases relevant to aging.
Highlights
When calorie intake is reduced by 20–30%, lifespan is extended by 20% or more in many model organisms, such as mice, flies, fish, spiders, etc. [13,14]
Using the Edmonton Frailty Scale (EFS) as a guide, our study identified 15 blood metabolites involved in antioxidation, cognition, and mobility as frailty markers (Figure 3) [56], while studies based on the Fried Cardiovascular Health Study Index (CHS) reported blood metabolites related mainly to physical or sarcopenic frailty [89]
Using the EFS as a guide, our study identified 15 blood metabolites involved in anti oxidation, cognition, and mobility as frailty markers (Figure 3) [56], while studies based
Summary
The genetic manipulation to extend the lifespan is known to be accompanied with the increase of antioxidants; for example, glutathione has been elevated in super Arf/p53 mice, a longevity model [12]. A recent report suggested that the modulation of FOXO via peptide intervention induces elimination of senescent cells in vivo, followed by healthy lifespan [23] Metabolites modulating these signaling pathways are effective both for extension of organismal lifespan in experimental models and for treatment of human diseases of aging: Resveratrol (activator of sirtuins) against obesity, rapamycin (inhibitor for Tor kinase) as an anti-cancer drug or immunosuppressor, and metformin (activator for AMPK) in diabetic therapy [17,24,25,26]. Metabolites could be a promising strategy for intervention against aging
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