Insulin/IGF-1 Signaling (IIS) Pathway: Difference between revisions

Insulin/IGF-1 Signaling (IIS) Pathway (view source)

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-The '''Insulin/IGF-1 Signaling (IIS) pathway''' is a significant area of study in the field of longevity and aging research. This pathway is known to play a critical role in the regulation of lifespan across various species, including ''C. elegans'', ''Drosophila melanogaster'', and ''Mus musculus''. Understanding the IIS pathway provides insights into the mechanisms of aging and potential interventions for age-related diseases.
+= Insulin/IGF-1 Signaling (IIS) Pathway and Longevity =
-==Overview==
-The IIS pathway is primarily involved in the regulation of growth, development, metabolism, and lifespan. It is activated by the binding of insulin and insulin-like growth factors (IGF) to their respective receptors, leading to a cascade of intracellular events. The pathway influences various cellular processes such as glucose metabolism, protein synthesis, and stress resistance.
+The '''Insulin/IGF-1 Signaling (IIS) pathway''' is a significant biochemical pathway that has been extensively studied in the context of aging and longevity. This pathway, conserved across various species, plays a critical role in regulating lifespan, stress resistance, and metabolism.
-==Key Components==
-*'''Insulin and IGF-1 Receptors''': These receptors are activated upon binding with insulin and IGF-1.
+== Overview ==
-*'''PI3K (Phosphoinositide 3-kinase)''': PI3K is activated by insulin and IGF-1 receptors, leading to the activation of downstream signaling molecules.
+The IIS pathway is primarily known for its function in glucose metabolism, growth, and development. It is activated by the binding of insulin and insulin-like growth factors (IGF) to their respective receptors, triggering a cascade of intracellular signaling events. This pathway's significance in longevity research was first highlighted in ''Caenorhabditis elegans'' and subsequently in other model organisms, including ''Drosophila melanogaster'' (fruit flies) and mice.
-*'''AKT/PKB (Protein Kinase B)''': AKT is a critical kinase in the pathway, promoting growth and survival signals.
-*'''FOXO (Forkhead box O) Transcription Factors''': FOXO factors are negatively regulated by the IIS pathway and are crucial in stress resistance and longevity.
+== Mechanism ==
-==Role in Longevity==
+{{main|Insulin signaling pathway}}
-Several studies have shown that reduced IIS signaling can lead to an extended lifespan in various organisms. This is primarily due to the enhanced stress resistance and altered metabolism resulting from decreased IIS activity.
+The pathway involves several key components:
-===''C. elegans'' Studies===
+* '''Insulin and IGF-1 Receptors:''' These receptors, upon activation by insulin or IGF-1, initiate the signaling cascade.
-In ''Caenorhabditis elegans'', mutations in the ''daf-2'' gene, which encodes an insulin/IGF-1 receptor, lead to a significant increase in lifespan. This effect is mediated through the downstream ''daf-16'' gene, a homolog of the FOXO family of transcription factors.
+* '''PI3K-Akt Pathway:''' Activation of PI3K (phosphoinositide 3-kinase) leads to the activation of Akt, a critical kinase in this pathway.
-===Mammalian Models===
+* '''FOXO Transcription Factors:''' Akt negatively regulates FOXO transcription factors, which are involved in stress resistance and longevity.
-In mice, reduced IGF-1 signaling has been associated with extended lifespan and improved healthspan. Similar findings have been observed in other mammalian models, suggesting a conserved mechanism of lifespan regulation through the IIS pathway.
+* '''mTOR Complex:''' The mTOR (mechanistic target of rapamycin) complex, another downstream target, is involved in cell growth and autophagy, processes crucial for aging.
-==Potential Therapeutic Implications==
-The manipulation of the IIS pathway offers potential therapeutic avenues for age-related diseases, including diabetes, neurodegenerative diseases, and cancer. Pharmacological agents that can modulate this pathway may have significant implications in promoting healthy aging and longevity.
+== Role in Longevity ==
-==References==
+Research in model organisms has shown that reducing IIS pathway activity can lead to increased lifespan and enhanced resistance to various stresses. In ''C. elegans'', mutations that reduce the function of the daf-2 gene, which encodes an insulin/IGF-1 receptor, result in a significantly extended lifespan{{pmid|8020096}}. Similarly, in fruit flies, reduced IGF signaling is associated with increased lifespan{{pmid|12524541}}.
-[[Category:Pathways]]
+== Human Relevance ==
+The implications of the IIS pathway in human aging are an area of active research. Variations in genes related to this pathway, such as the FOXO3 gene, have been associated with longevity in human populations{{pmid|18516045}}. However, the exact mechanisms and potential for therapeutic intervention in humans remain to be fully elucidated.
+== Research and Therapeutic Potentials ==
+There is ongoing research into pharmacological agents that can modulate the IIS pathway to potentially extend healthy lifespan. Drugs like metformin and rapamycin, which indirectly influence this pathway, are of particular interest in longevity research{{pmid|30428338}}.
+== Conclusion ==
+The Insulin/IGF-1 Signaling pathway is a cornerstone in the study of the molecular biology of aging. Its conservation across species and clear influence on lifespan and healthspan make it a critical target for aging research. Future studies and clinical trials are expected to further clarify its role in human aging and potential for therapeutic interventions.