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Nutrient sensing, macronutrient restriction and dietary composition manipulation
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Which dietary amino acids, when restricted or supplemented, promote increased healthspan and/or longevity? How does dietary protein quantity and quality interact with the level and type of other dietary macronutrients to influence healthspan and longevity? How do sex and genetic background contribute to the response to altered dietary macronutrient composition, and can we identify genetic loci that define the response to specific dietary macronutrients? Do changes in dietary macronutrients promote healthy aging through engaging with canonical signaling pathways (mTOR, GCN2, FGF21)? Does the timing of macronutrient intake contribute to the effects of those macronutrients on healthspan and longevity? Do ketone bodies contribute to increases in longevity and healthspan with calorie restriction, intermittent fasting and time-restricted feeding? Are certain dietary nutrients better utilized and digested at specific circadian times?
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Circadian rhythms and dietary interventions in healthspan promotion
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Are the effects of time-restricted-feeding interventions mediated by prolonged fasting between meals, reinforced circadian cycles? How do natural feeding patterns, which can vary greatly between and within individuals day-to-day, and the mechanisms that govern them influence responses to dietary interventions? Why do circadian disruptions, including sleep disruption, affect whole body metabolism and healthspan? Is circadian resilience (e.g., both amplitude enhancement and phase adaptation) a key mechanism underlying dietary/fasting effects to promote healthspan, and if so, what regulators are involved? How do different time-restricted feeding regiments affect microbiome composition and its metabolites?
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Macronutrient manipulation in tissue homeostasis and organ function
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Which lipids and lipid-derived molecules promote or hinder healthspan? Do macronutrient requirements change with age? Do older adults need more proteins and dietary fiber? What are the metabolic and energetic demands of different tissues and how does aging impact the metabolic flexibility across tissues? Does nutrient transport and uptake change with age? How do different cell types within the same tissue shape the microenvironment and determine their metabolic preferences and flexibility?
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Translational promises and challenges of dietary interventions to enhance human healthspan
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Can alterations in dietary macronutrients or time of feeding promote healthspan in non-human primates? Are the effects of time-restricted-feeding interventions in humans mediated by prolonged fasting between meals and/or reductions in calorie intake? How do interventions targeting quality, quantity and timing of nutrition during pregnancy and/or lactation affect maternal health and child’s long-term health? Time-restricted feeding often reduces calorie intake, which can be undesirable for older adults at risk for sarcopenia. Can TRF with optimum nutrition reduce frailty and improve healthspan among older adults? How do sex differences and sex hormones affect the response to nutrient restrictions and dietary manipulation? Do males and females and pre-menopause and postmenopause women need specific dietary intervention for increasing healthspan? How does exercise and energy balance impact beneficial effects of dietary interventions?
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