Recognize that cycling between anabolic and catabolic states is potentially the single most important factor for cellular health and longevity, as both too little and too much mTOR activity or autophagy can be toxic.
If considering rapamycin for longevity, an intermittent dosing approach is recommended to induce a relatively weak autophagy and allow the system to rebuild, aligning with the crucial principle of anabolism-catabolism cycling.
Explore methionine restriction as a dietary intervention for beneficial effects on glucose homeostasis and lifespan extension, as it significantly drops during fasting and its metabolite, SAM, directly inhibits the mTOR pathway when reduced.
To broadly impact cellular state, rejuvenate cells, and slow aging, target mTOR because it acts as a ‘general contractor’ for the cell, influencing numerous processes simultaneously, which is more effective than targeting individual pathways.
Do not completely inhibit mTORC1 as it is essential for the growth of normal cells; full inhibition would mimic a crude chemotherapeutic agent, leading to atrophy and cell death.
Understand that leucine (and to a lesser extent isoleucine, but not valine in their findings) and arginine directly activate mTORC1 by binding to intracellular receptors, signaling nutrient availability and driving anabolism.
Be aware that while mTOR modulation can mimic some effects of fasting, systemic nutrient levels remain high, potentially leading to nutrient accumulation in cells, unlike actual fasting where nutrient levels are lower.
Be aware that the beneficial effects of methionine restriction, which work by reducing SAM and inhibiting mTOR, could potentially be bypassed or counteracted by supplementing with SAM (S-adenosylmethionine).
Recognize that both glucose and insulin activate mTORC1 through independent pathways, which aligns with its role as a nutrient sensor, signaling a fed state.
Understand that mTORC1 activity is regulated by a wide array of cellular conditions, including nutrients, oxygen levels, pH, growth factors, and osmotic pressure, making it a central hub for cellular state sensing.
When assessing the body’s anabolic/catabolic state, consider both global signals (like insulin reflecting overall organismal fed state) and local signals (like specific nutrient availability within cells) as mTOR integrates both.
While rapamycin is an immunosuppressant, it appears to have direct anti-cancer effects that can mitigate the increased cancer risk from immune suppression, potentially by affecting the growth and immune evasion of existing cancer cells rather than preventing initial mutations.
Allow individuals, especially students, complete freedom to pursue their own projects, as this can be a foundational experience for developing into an independent scientist or professional.