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Deregulated Nutrient Sensing: Difference between revisions
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'''Deregulated nutrient sensing''' is one of the hallmarks of aging, characterized by the dysregulation in the mechanisms that cells and organisms use to detect and respond to nutrients. Nutrient sensing pathways play a crucial role in maintaining metabolic homeostasis and influence key processes related to growth, development, reproduction, and longevity. As organisms age, the efficiency and accuracy of these pathways often decline, leading to impaired metabolic responses and contributing to age-related diseases and decreased lifespan. | '''Deregulated nutrient sensing''' is one of the hallmarks of aging, characterized by the dysregulation in the mechanisms that cells and organisms use to detect and respond to nutrients. '''Nutrient sensing pathways''' play a crucial role in maintaining metabolic homeostasis and influence key processes related to growth, development, reproduction, and longevity. As organisms age, the efficiency and accuracy of these pathways often decline, leading to impaired metabolic responses and contributing to age-related diseases and decreased lifespan. | ||
==Key Nutrient Sensing Pathways== | ==Key Nutrient Sensing Pathways== | ||
Nutrients are substances needed by the body to sustain basic functions in order to survive, grow, and reproduce and are optimally obtained by eating a balanced diet. Thus, glucose and other carbohydrates, amino acids, and lipids are essential cellular nutrients with certain mechanisms to sense their availability in mammalian cells. The capability to sense and respond to variations in the environmental nutrient availability is a key requisite for survival. Thus, cells must be able to store nutrients when they are abundant and access them when they are scarce. Moreover, nutrient levels in the circulation need to stay within certain safe ranges. Therefore, cells must be able to sense nutrient levels in order to react appropriately. Various pathways that sense intracellular and extracellular levels of carbohydrates, amino acids, lipids, and different metabolites are integrated and coordinated at the organismal level via hormonal signals. Throughout food abundance, nutrient-sensing pathways employ anabolism and storage, whereas food scarcity activates homeostatic mechanisms.{{pmid|25592535}} | |||
There are four nutrient sensing pathways: IIS, mTOR, AMPK and Sirtuins. The IIS and mTOR pathways indicate nutrient abundance, so downregulating them prolongs the lifespan by reducing cell growth and anabolic metabolism. On the other hand, the AMPk and sirtuin pathways imply nutrient scarcity, so their upregulation prolongs lifespan by reducing nutrient sensing, thus imitating dietary restriction. | |||
*'''Insulin and IGF-1 Signaling (IIS)''': IIS is crucial for controlling growth and metabolism in response to nutrient availability. Dysregulation of IIS is associated with various metabolic disorders, including diabetes and obesity, and modulating this pathway has been shown to affect lifespan in various organisms. | *'''Insulin and IGF-1 Signaling (IIS)''': IIS is crucial for controlling growth and metabolism in response to nutrient availability. Dysregulation of IIS is associated with various metabolic disorders, including diabetes and obesity, and modulating this pathway has been shown to affect lifespan in various organisms. | ||
*'''mTOR Pathway''': The mechanistic target of rapamycin (mTOR) pathway integrates signals from nutrients, growth factors, and energy status to regulate growth, protein synthesis, and autophagy. Overactivation of mTOR is linked to accelerated aging and age-related diseases, while its inhibition has been associated with lifespan extension. | *'''mTOR Pathway''': The mechanistic target of rapamycin (mTOR) pathway integrates signals from nutrients, growth factors, and energy status to regulate growth, protein synthesis, and autophagy. Overactivation of mTOR is linked to accelerated aging and age-related diseases, while its inhibition has been associated with lifespan extension. | ||