#1

This recent presentation at ARDD assess CR in mice under various regime including day and night and 2 hour vs 12 eating CR. [Joseph Takahashi at ARDD2024: Circadian Clock Regulation of Aging and Longevity - YouTube](https://www.youtube.com/watch?v=o10aZnpcEXA&t=717s)
Fairly clear that circadian alignment is very important, but CR and TRE are too.
Associated paper: [https://pmc.ncbi.nlm.nih.gov/articles/PMC9262309/pdf/nihms-1820506.pdf]

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#2

An interesting paper:

Caloric restriction (CR) prolongs lifespan, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour-feeding and 22-hour-fasting, raising the question whether calories, fasting, or time of day are causal. We show that 30%-CR
is sufficient to extend lifespan 10%; however, a daily fasting interval and circadian-alignment
of feeding act together to extend lifespan 35% in male C57BL/6J mice. These effects are independent of body weight. Aging induces widespread increases in gene expression associated with inflammation and decreases in expression of genes encoding components of metabolic pathways in liver from ad lib fed mice. CR at night ameliorates these aging-related changes. Thus, circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.

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#3

IIRC the challenge is how to translate this to humans. It seems logical that mouse circadian rhythm would align with the sun, similar to humans, so one might translate it directly as time restricted feeding. However, their aging/metabolism is much faster, so 22 hours for a mouse is more like days for a human, corresponding to multi day fasts. Which one is right?

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#4

Mice are nocturnal. They are naturally active at night.

#5

Accepting that point as an important distinction I would think, for any creature that sleeps, during sleeping time is the best time to have processes of autophagy etc. That is because there will be less energy available whilst recycling cell components.

I think we see that when people feel tired after taking Rapamycin or Urolithin A.

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#6

Yes, they have faster metabolism. But they have one eating window per day, ideally during their night active cycle as the study shows. I don’t see the 2-hour eating window as something for humans to mimic but it suggests that windows tighter than 12 hours per day are better. It’s a directional signal. I try to eat within 7 to 8 hours a day, from around 10:30a to 5:30p. For me, a side benefit is much better sleep by not eating after dark.

#7

To me this opens the door to examining many more potential experimental flaws. Like the spectrum of lighting for example. And were mice allowed full darkness?
Also, we now know that many past CR experiments with mice/rats are confounded by time restricted eating as they wolf down their meal in a small-time window when given all their food at once. And as shown in Dr. Takahashi’s work, confounded by circadian misalignment. Work from the Lamming Lab showed (circa 2021) that a lot of benefits attributed to CR (in mice) is actually due to TRF, but that gene expression changes were not identical. I suspect that mild CR combined with moderate TRE (during daylight hours) is closer to optimum and more actionable by humans.