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Deregulated Nutrient Sensing: Difference between revisions
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*'''AMP-Activated Protein Kinase (AMPK)''': AMPK is activated under low energy conditions and helps restore energy balance by promoting catabolic processes and inhibiting anabolic processes. It plays a critical role in maintaining energy homeostasis and is considered a key target for treating metabolic diseases. | *'''AMP-Activated Protein Kinase (AMPK)''': AMPK is activated under low energy conditions and helps restore energy balance by promoting catabolic processes and inhibiting anabolic processes. It plays a critical role in maintaining energy homeostasis and is considered a key target for treating metabolic diseases. | ||
*'''[[Sirtuins]]''': Sirtuins are NAD+-dependent deacetylases that respond to changes in the cellular energy state and regulate various metabolic processes, including the response to calorie restriction. They are implicated in the aging process and the development of age-related diseases. | *'''[[Sirtuins]]''': Sirtuins are NAD+-dependent deacetylases that respond to changes in the cellular energy state and regulate various metabolic processes, including the response to calorie restriction. They are implicated in the aging process and the development of age-related diseases. | ||
Amino acids regulate multiple interacting nutrient sensing pathways. The adequate sensing of amino acid availability is significant for the effective regulation of protein synthesis and catabolism. An important way of amino acid control for nutrient sensing is via the amino acid sensing taste receptors, members of the T1R and T2R families of G-protein-coupled receptors. Amino acid taste receptors in humans exhibit a high affinity to glutamate, with other L-amino acids also acting as ligands.{{pmid|11894099}}{{pmid|25592535}} | |||
==Consequences of Deregulated Nutrient Sensing== | ==Consequences of Deregulated Nutrient Sensing== | ||
Deregulated nutrient sensing can lead to several adverse effects on health and longevity: | Deregulated nutrient sensing can lead to several adverse effects on health and longevity: | ||
*'''Insulin resistance''': One of the predominant nutrient sensing dysfunctions that occur upon human aging is insulin resistance. This condition emerges due to factors such as oxidative stress, inflammation, enzymatic activity disorders, and fatty acids accumulation, contributing to a decline in insulin sensitivity. As a consequence, the body gradually loses its capability to regulate blood sugar level, exacerbating conditions like atherosclerosis and fatty liver disease.<ref>What Is Deregulated Nutrient Sensing? https://www.gowinglife.com/what-is-deregulated-nutrient-sensing-the-hallmarks-of-ageing-series/ (accessed Mar 20, 2023).</ref> | |||
*'''Metabolic Disorders''': Dysregulation can contribute to the development of metabolic diseases such as diabetes, obesity, and metabolic syndrome. | *'''Metabolic Disorders''': Dysregulation can contribute to the development of metabolic diseases such as diabetes, obesity, and metabolic syndrome. | ||
*'''Decreased Adaptability''': Impaired nutrient sensing reduces the organism's ability to adapt to changes in nutrient availability, leading to suboptimal metabolic responses and increased vulnerability to environmental changes. | *'''Decreased Adaptability''': Impaired nutrient sensing reduces the organism's ability to adapt to changes in nutrient availability, leading to suboptimal metabolic responses and increased vulnerability to environmental changes. | ||
*'''Accelerated Aging''': Deregulated pathways are associated with accelerated cellular and organismal aging, promoting age-related phenotypes and reducing lifespan. | *'''Accelerated Aging''': Deregulated pathways are associated with accelerated cellular and organismal aging, promoting age-related phenotypes and reducing lifespan. | ||
*'''Age-related Diseases''': Dysregulation is implicated in the pathogenesis of various age-related diseases, including cancer, [[Neurodegenerative Disorders|neurodegenerative disorders]], and cardiovascular diseases. | *'''Age-related Diseases''': Dysregulation is implicated in the pathogenesis of various age-related diseases, including cancer, [[Neurodegenerative Disorders|neurodegenerative disorders]], and cardiovascular diseases. | ||
==Therapeutic Interventions== | ==Therapeutic Interventions== | ||
Modulating nutrient sensing pathways offers potential therapeutic avenues for extending healthspan and treating age-related diseases: | Modulating nutrient sensing pathways offers potential therapeutic avenues for extending healthspan and treating age-related diseases: | ||
*'''Dietary Interventions''': Calorie restriction and intermittent fasting have been shown to beneficially modulate nutrient sensing pathways, leading to improved health and longevity. | *'''Dietary Interventions''': Calorie restriction and intermittent fasting have been shown to beneficially modulate nutrient sensing pathways, leading to improved health and longevity.<ref>{{pmid|25815989}}</ref> | ||
*'''Pharmacological Agents''': Drugs targeting these pathways, such as metformin (AMPK activator), rapamycin (mTOR inhibitor), and sirtuin activators, are being explored for their potential to mimic the beneficial effects of dietary interventions and treat age-related metabolic disorders. | *'''Pharmacological Agents''': Drugs targeting these pathways, such as metformin (AMPK activator), rapamycin (mTOR inhibitor), and sirtuin activators, are being explored for their potential to mimic the beneficial effects of dietary interventions and treat age-related metabolic disorders. | ||
*'''Lifestyle Modifications''': Exercise and dietary adjustments can influence the activity of nutrient sensing pathways and are recommended for maintaining metabolic health and preventing age-related diseases. | *'''Lifestyle Modifications''': Exercise and dietary adjustments can influence the activity of nutrient sensing pathways and are recommended for maintaining metabolic health and preventing age-related diseases. | ||