Basic helix-loop-helix ARNT-like protein 1

The individual neurons keep time through a molecular feedback loop involving a set of proteins known as clock proteins.

The core clock genes include a gene called Clock, a gene called BMAL1, and two families of genes called Period and Cryptochrome.

During the day, the Clock and BMAL1 proteins bind together and activate the Period and Cryptochrome genes, causing the cell to produce Period and Cryptochrome proteins.

As these proteins accumulate, they eventually inhibit Clock and BMAL1, shutting down their own production.

The Period and Cryptochrome proteins then gradually degrade over time, lifting the inhibition and allowing Clock and BMAL1 to start the cycle again.

This entire molecular loop takes approximately twenty-four hours to complete, which is why it is called a circadian rhythm, from the Latin words circa meaning about and dies meaning day.

Without any external time cues, such as sunlight or alarm clocks, the human circadian clock runs on a cycle that is slightly longer than twenty-four hours, typically around twenty-four hours and ten to twenty minutes.

The individual neurons keep time through a molecular feedback loop involving a set of proteins known as clock proteins.

The core clock genes include a gene called Clock, a gene called BMAL1, and two families of genes called Period and Cryptochrome.

During the day, the Clock and BMAL1 proteins bind together and activate the Period and Cryptochrome genes, causing the cell to produce Period and Cryptochrome proteins.

As these proteins accumulate, they eventually inhibit Clock and BMAL1, shutting down their own production.

The Period and Cryptochrome proteins then gradually degrade over time, lifting the inhibition and allowing Clock and BMAL1 to start the cycle again.

This entire molecular loop takes approximately twenty-four hours to complete, which is why it is called a circadian rhythm, from the Latin words circa meaning about and dies meaning day.

Without any external time cues, such as sunlight or alarm clocks, the human circadian clock runs on a cycle that is slightly longer than twenty-four hours, typically around twenty-four hours and ten to twenty minutes.

So skin runs peripheral clocks.

So keratinocytes, fibroblasts, sebocytes, they express clock genes such as BMAL1, clock, PER, P-E-R.

Some people, I call it PER.

And so the measurable rhythms, they're real, they're reproducible.

All right, Dr. Kuipers, where does chronobiology fit into this discussion on the metabolic side?

So circadian transcription factors like CLOCK and BMAL1 drive the expression of NAMPT, the rate-limiting enzyme in the NAD+ salvage pathway.

So when circadian rhythms are disrupted by late-night artificial light or shift work, NAMPT oscillations flattens.

Cellular NAD+ pools contract, and Sirt1 activity drops.

Dr. Ted, you get round two.

Yes, you cannot supplement out of circadian misalignment.

BMAL1 drives NAMPT.

Light anchoring comes first.