mTORC1

And it's really the garbage collection that will end up determining our health and our lifespan.

TORC1 controls fasting-induced ketogenesis.

You want to produce ketones? It's going to be controlled by TOR.

You have to keep it low.

Keep TOR low, you'll produce ketones.

Everything goes through TOR.

Inhibition of TORC1 is required for the fasting-induced activation of PPAR-alpha, which is the transcriptional factor that induces ketogenic genes.

Major pathway by which amino acids control TOR is distinct from that of insulin.

Now in T cells, typically we talk about reprogramming because they are exiting quiescence.

Now mTOR complex like mTORC1 is required for cell cycle entry and the coordination of early metabolic changes.

that must occur upon T-cell activation.

T-cells deficient in Raptor, now that's a protein, that's an essential component of the mTORC1, they fail to upregulate the expression of glucose transporter 1 and glycolytic enzymes when activated.

So raptor deficient T cells also exhibit defects in de novo lipid biosynthesis, oxidative phosphorylation as well, suggesting that mTORC pathway is a global regulator of T cell metabolic programming.

And upon activation to follow suit with this premise, mTORC1 regulates T cell metabolism in fully differentiated effector T cell populations.

Now, raptor deficiency leads to impaired lipid synthesis and impaired mitochondrial respiration.

This has been shown in Tregs, B follicular helper T cells, although these results are modal dependent.

And that interaction interfered with ATP synthase assembly.

So ATP production fell, mTORC1 signaling fell, and adipogenesis, the creation and expansion of fat cells, was thus suppressed.

But here's where it gets really interesting.

In human fat samples from people with obesity, higher amounts of mitochondrial break were associated with poorer mitochondrial bioenergetic function.

The cell senses low energy, so it stops dividing, stops trying to build new tissue, and flips into a deep maintenance and repair mode.

The smartphone entering low battery mode is exactly what's happening because when that AMPK sensor is activated, it subsequently shuts down a different pathway called mTORC1.

And what does that do?

To explain how it does this, think of the cell's nucleus like an exclusive VIP club.

Metformin basically tells the bouncers at the door, the nuclear pore complex, to block a specific messenger protein from getting inside.

Oh, interesting.

Because that messenger can't get in, mTORC1 is suppressed.

The cell stops synthesizing new proteins and instead triggers a process called autophagy.

Scientists at the University of Bonn reprogrammed blood cell precursors from an 80-year-old into neural stem cells with a molecular age below 20 inside the lab.

A new RLX201 serum targeting mTORC1 improved skin firmness and wrinkle scores by 21% and texture by 40% from baseline in a 12-week trial of 47 women, with no adverse events reported.

Okay, so from the research that I've done, that's a little bit overstated.

Mm-hmm.