A Common Root Cause Of Chronic Diseases? (Why Many Longevity Meds Treat Diabetes) READ SUMMARY BELOW
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- Опубликовано: 6 фев 2025
- We store calories from our diet in adipocytes. However, excessive calorie intake eventually overwhelms our adipocytes capacity to store energy, resulting in excess energy from our diet being stored in other tissues (called ectopic fat). One of the tissues that accumulate ectopic fat is Skeletal Muscle, which store the excess energy from our diet as IntraMyoCellular Lipids (The Liver also stores this excess energy, causing MAFLD).
Normally, Insulin signals Skeletal Muscle to use blood glucose as a source of energy. However, when Skeletal Muscles accumulate IntraMyoCellular Lipids, they resist insulin's signal to uptake and use blood glucose as a source of energy(this is insulin resistance) because they already have IntraMyoCellular Lipid as a source of energy. When skeletal muscle becomes insulin-resistant, glucose remains elevated in the blood, triggering the pancreas to respond with compensatory hyperinsulinemia, which may accelerate the onset of age-related disease.
Blood Insulin interacts with virtually every cell in our body by activating the mTOR pathway, which is at the center of regulating the rate of aging. The 3 interventions that most reproducibly extend longevity in virtually all animal models are Calorie Restriction, Rapamycin, IGF-Receptor Mutation. All these interventions extend longevity by INHIBITING mTOR, however hyperinsulinemia ACTIVATES mTOR, and may explain why hyperinsulinemia is one of the most predictive markers of all-cause mortality (accelerates rate of aging). Insulin also affects FOXO, the prototypical gene variant associated with longevity in population studies. This may explain why a large percentage of medications proven successful in the Nation Institute of Health "Intervention Testing Program" are Type-II Diabetes medications that reduce blood glucose, which ultimately reduces hyperinsulinemia and mTOR activity. However, insulin is still recommended for diabetics because hyperglycemia significantly affects quality of life (i.g. blindness, amputation), and Hyperglycemia results in advanced glycated end products which theoretically accelerate aging. Therefore, the ideal scenario is lifestyle management to address the root cause of hyperglycemia AND hyperinsulinemia. The link below goes into more details on mTORs role in aging.
• The Biology of Aging &...
Excessive insulin provides cells with pro-growth signals, enabling PRE-cancerous cells continued cell division and further accumulation of mutations. This is because insulin's “pro-growth” signals blunt the pro-apoptosis signals responding from DNA damage, allowing further cell proliferation and accumulation of DNA mutations in precancerous cells that SHOULD activate apoptosis due to excessive DNA mutation signals. Insulin activates mTOR, which up-regulates mitochondrial HK2, which functions to inhibit BAX, thus effectively preventing upstream DNA damage signals from inducing apoptosis through BAX, in precancerous cells. mTOR inhibits AMPK, which down-regulates HK2. Insulin increases free IGF-1, which interferes multiple control points of apoptosis.
Also, mouse models genetically modified for the ability to induce high rates of DNA mutations show we’ve evolved remarkably efficient systems designed to prevent accumulation of DNA damage and precancerous cells, however carcinogen exposure coupled with attenuated repair systems (e.g. unregulated hyperinsulinemia blunting apoptosis) allow gradual accumulation of cells with DNA mutations that produce a malignancy that becomes unmanageable. Elephants have 4 quadrillion cells but lower cancer rates than humans, they also have x20 more copies of p53 than humans (most common mutation in human cancer), as reduced p53 activity permits oncogenesis. Insulin activated mTOR induces MDM2 translation which down-regulates p53, leading to chronic inhibition of natural cellular repair systems. I believe larons syndrome, metformin, and calorie restriction create time-intervals where PRE-cancerous cells are primed for apoptosis and removal, BUT CAN NOT TREAT MATURE MALIGNANCIES WHICH HAVE ALREADY DEVELOPED THE ONCOGENES THAT CAUSE UNREGULATED CELL PROLIFERATION, UNLESS TREATED WITH CYTOTOXIC INTERVENTIONS SUCH AS CHEMO, RADIATION, IMMUNOTHERAPY.
Some argue that MAFLD (ectopic fat in liver) produces metabolites (acetyl-coa) that activate enzymes resulting in up-regulating gluconeogenesis, therefore contributing to hyperinsulinemia. I believe visceral fat is “associated” with Metabolic Syndrome because it’s a proxy for Ectopic fat in Skeletal Muscle and Liver.
There are many factors not related to insulin that influence Coronary Artery Diseases, most importantly ApoB (proxy for LDL and atherogenic particle count). However, Obesity, IMCL, and Hyperinsulinemia affect lipoprotein dynamics and residence time. However, it’s important to emphasize there are many factors contributing to CAD, such as endothelial inflammation, oxLDL and Lp(a).
Hey Joe, congrats on making it to your 4th year in medical school. Best of luck to you in the future. Legions of MCAT takers have used your videos and your insight to score well on the MCAT, and we all thank you for it. Have a good one!
Hey, that's pretty good! Your videos helped me get into Med school! Glad to see you're still shining on your light my friend! Never change : )
Its great that you are back ❤️❤️❤️
Bro I am still using you vedios to get through the MCAT , thank you
Remember the kindness the Lord shows us where-ever we go. The Lord is like a rock, whoever believes in Him will never scatter for help, because they trust in the LORD. Good and upright is our God and highly to be praised. whoever is baptized in the name of the trinity, and believes the son of man, will saved.
Welcome back!!! Your videos have been amazing
Our goat has returned. Thank you for all your videos 🐐
This was extremely interesting
Great video! What software/hardware do you use for your videos? I have a hard time making some programs work.
Hi Joe!! can you please share your procreate settings? I want to take notes and make mind maps w procreate but i can't seem to figure out the canvas size and stuff
my goat
MVP