Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or accelerated by a decline or loss of responsiveness to activation of the energy-sensing protein AMPK, a critical gerosuppressor of mTOR. The occurrence of age-related diseases, therefore, reflects the synergistic interaction between our evolutionary path to sedentarism, which chronically increases a number of mTOR activating gero-promoters (e.g., food, growth factors, cytokines and insulin) and the "defective design" of central metabolic integrators such as mTOR and AMPK. Our laboratories at the Bioactive Food Component Platform in Spain have initiated a systematic approach to molecularly elucidate and clinically explore whether the "xenohormesis hypothesis," which states that stress-induced synthesis of plant polyphenols and many other phytochemicals provides an environmental chemical signature that upregulates stress-resistance pathways in plant consumers, can be explained in terms of the reactivity of the AMPK/mTOR-axis to so-called xenohormetins. Here, we explore the AMPK/mTOR-xenohormetic nature of complex polyphenols naturally present in extra virgin olive oil (EVOO), a pivotal component of the Mediterranean style diet that has been repeatedly associated with a reduction in age-related morbid conditions and longer life expectancy. Using crude EVOO phenolic extracts highly enriched in the secoiridoids oleuropein aglycon and decarboxymethyl oleuropein aglycon, we show for the first time that (1) the anticancer activity of EVOO secoiridoids is related to the activation of anti-aging/cellular stress-like gene signatures, including endoplasmic reticulum (ER) stress and the unfolded protein response, spermidine and polyamine metabolism, sirtuin-1 (SIRT1) and NRF2 signaling; (2) EVOO secoiridoids activate AMPK and suppress crucial genes involved in the Warburg effect and the self-renewal capacity of "immortal" cancer stem cells; (3) EVOO secoiridoids prevent age-related changes in the cell size, morphological heterogeneity, arrayed cell arrangement and senescence-associated β-galactosidase staining of normal diploid human fibroblasts at the end of their proliferative lifespans. EVOO secoiridoids, which provide an effective defense against plant attack by herbivores and pathogens, are bona fide xenohormetins that are able to activate the gerosuppressor AMPK and trigger numerous resveratrol-like anti-aging transcriptomic signatures. As such, EVOO secoiridoids constitute a new family of plant-produced gerosuppressant agents that molecularly "repair" the aimless (and harmful) AMPK/mTOR-driven quasi-program that leads to aging and aging-related diseases, including cancer.

This paper provides an overview of alternatives to conventional thermal treatments and a review of the literature on fruit-juice processing for three key operations in fruit-juice production such as microbial inactivation, enzyme inactivation, and juice yield enhancement, these being radiation treatments (UV light, high-intensity light pulses, γ-irradiation), electrical treatments (pulsed electric fields, radiofrequency electric fields, ohmic heating), microwave heating, ultrasound, high hydrostatic pressure, inert gas treatments (supercritical carbon dioxide, ozonation), and flash-vacuum expansion. The nonthermal technologies discussed in this review have the potential to meet industry and consumer expectations. However, the lack of standardization in operating conditions hampers comparisons among different studies, and consequently ambiguity arises within the literature. For the juice industry to advance, more detailed studies are needed on the scaling-up, process design, and optimization, as well as on the effect of such technologies on juice quality of juices in order to maximize their potential as alternative nonthermal technologies in fruit-juice processing.

Traditional thermal techniques may cause losses in nutritional quality and phytochemical contents, and also in physicochemical, rheological, and organoleptic properties of processed fruit juices. This paper provides an overview of the effect on these qualities by the use of alternatives to traditional thermal treatments in fruit-juice processing, for three key operations in fruit-juice production such as microbial inactivation, enzyme inactivation, and juice-yield improvement. These alternatives are UV light, high-intensity light pulses, γ-irradiation, pulsed electric fields, radiofrequency electric fields, Ohmic heating, microwave heating, ultrasound, high hydrostatic pressure, supercritical carbon dioxide, ozonation, and flash-vacuum expansion. Although alternatives to heat treatments seem to be less detrimental than the thermal treatment, there are many parameters and conditions that influence the output, as well as the nature of the juice itself, hampering comparisons between different studies. Additionally, future research should focus on understanding the mechanisms underlying the changes in the overall quality of fruit juices, and also on scaled-up processes, process design, and optimization that need to be deal with in detail to maximize their potential as alternative nonthermal technologies in fruit-juice processing while maintaining fruit-juice attributes to the maximum.

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Edited by Jeffrey E. Pessin Patients with fatty liver diseases present altered mitochondrial morphology and impaired metabolic function. Mitochondrial dynamics and related cell function require the uncleaved form of the dynamin-like GTPase OPA1. Stabilization of OPA1 might then confer a protective mechanism against stress-induced tissue damages. To study the putative role of hepatic mitochondrial morphology in a sick liver, we expressed a cleavage-resistant long form of OPA1 (L-OPA1⌬) in the liver of a mouse model with mitochondrial liver dysfunction (i.e. the hepatocyte-specific prohibitin-2 knockout (Hep-Phb2 ؊/؊) mice). Liver prohibitin-2 deficiency caused excessive proteolytic cleav-ageofL-OPA1,mitochondrialfragmentation,andincreasedapoptosis. These molecular alterations were associated with lipid accumulation, abolished gluconeogenesis, and extensive liver damage. Such liver dysfunction was associated with severe hypoglycemia. In prohibitin-2 knockout mice, expression of L-OPA1⌬ by in vivo adenovirus delivery restored the morphology but not the function of mitochondria in hepatocytes. In prohibitin-competent mice, elongation of liver mitochondria by expression of L-OPA1⌬ resulted in excessive glucose production associated with increased mitochondrial respiration. In conclusion, mitochondrial dynamics participates in the control of hepatic glucose production. This work was supported by Swiss National Science Foundation Sinergia Grants CRSII3_147637 (to P. M. and J.-C. M.) and 310030_172862 (to M. F.) and by a fellowship from the Fundación Alfonso Martín Escudero (to C. J. S). The authors declare that they have no conflicts of interest with the contents of this article. This article was selected as one of our Editors' Picks. This article contains Tables S1 and S2 and Figs. S1-S8.

ScopeOlive-tree polyphenols have demonstrated potential for the management of obesity-related pathologies. We aimed to explore the capacity of Olive-tree leaves extract to modulate triglyceride accumulation and AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model.MethodsIntracellular triglycerides and AMPK activity were measured on the hypertrophic 3T3-L1 adipocyte model by AdipoRed and immunofluorescence microscopy, respectively. Reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) was used for the fractionation of the extract and the identification of the compounds. In-silico molecular docking of the AMPK alpha-2, beta and gamma subunits with the identified compounds was performed.ResultsOlive-tree leaves extract decreased the intracellular lipid accumulation through AMPK-dependent mechanisms in hypertrophic adipocytes. Secoiridoids, cinnamic acids, phenylethanoids and phenylpropanoids, flavonoids and lignans were the candidates predicted to account for this effect. Molecular docking revealed that some compounds may be AMPK-gamma modulators. The modulatory effects of compounds over the alpha and beta AMPK subunits appear to be less probable.ConclusionsOlive-tree leaves polyphenols modulate AMPK activity, which may become a therapeutic aid in the management of obesity-associated disturbances. The natural occurrence of these compounds may have important nutritional implications for the design of functional ingredients.