Circadian Biology: Genetics, Behavior, Metabolism, Light, Oxygen & Melatonin | Joseph Takahashi | 237

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How our biological clocks shape biology from the molecular to behavioral level.

Episode Summary: Dr. Joseph Takahashi discusses circadian rhythms, exploring their biological basis, from molecular mechanisms to their impact on metabolism and health; the discovery of circadian clock genes; role of the suprachiasmatic nucleus, and how light, feeding, and oxygen influence these rhythms. The conversation highlights practical implications, such as the effects of artificial light and meal timing on health, and touches on emerging research linking stronger circadian clocks to longevity.

About the guest: Joseph Takahashi, PhD is a renowned neuroscientist at UT Southwestern Medical Center, where he leads research on circadian clock genes.

Discussion Points:

• The suprachiasmatic nucleus in the hypothalamus acts as the brain's central clock, syncing with light via the retina.
• Key circadian genes like CLOCK and BMAL regulate thousands of genes, especially those involved in metabolism, impacting health outcomes.
• Internal desynchronization, when brain and organ clocks misalign (e.g., from eating at night), can lead to metabolic issues like pre-diabetes.
• In mice, eating at the right time (night for nocturnal animals) extends lifespan by up to 35% under caloric restriction, compared to 10% with spread-out feeding.
• Artificial light, especially blue light at night, disrupts melatonin and circadian rhythms, while natural sunlight supports healthy eye development.
• Melatonin, a darkness-signaling hormone, is best for resetting rhythms (e.g., jet lag) at low doses, not as a sedative, and U.S. supplements vary widely in quality.
• Oxygen-sensing proteins interact with circadian clock components, hinting at links between altitude, metabolism, and health.
• Learning and memory show diurnal variations, with better performance at certain times, influenced by circadian modulation of synaptic activity.
• A stronger circadian clock, created genetically in mice, led to 16% longer lifespan and resistance to weight gain (unpublished research).

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