What stood out here is how strongly the field is shifting from general ideas about timing to very precise, measurable mechanisms that could eventually shape how care is actually delivered.
Yes, that is exactly what we are going for here, Dr. Siddiqui. Thank you for pointing that out! I'm really curious, coming from an educator's perspective, what gaps do you see in your practice that I might be able to help with? Is there a set of articles or frameworks that would be helpful for you?
Excellent summary of what was discussed at the SRBR conference. Circadian biology needs to be better understood by primary care physicians who often just follow guidelines based approach and never a precision based care. This is what is lacking.
Human metabolism was never adequately taught in medical school curriculum. The understanding that human metabolism is a constant 'Flux' and not static is lacking across health care practitioners.
Understanding Circadian rhythms is crucial if we have to implement Medicine 3.0, aka., Precision medicine.
Recently there were two articles published by John's Hopkins researchers on RAR....'Rest Activity Rhythms' as a biomarker of biological aging.
People who had robust RAR's had reversed their biological age on various epigenetic clocks by several years. One cohort was in healthy older adults, whose Brain MRI's revealed improved Hippocampal volumes in those who followed robust RAR patterns.
Wrist based actigraphy data was used along with blood based DNA methylation clocks. RAR is being proposed as a biomarker to monitor rate of aging by those researches at Bloomberg school of public health at John's Hopkins.
Really great feedback, thank you for sharing your perspective, Dr. Lakkaraju, and for the article recommendation on RAR, that's a new one for me! I will dive into it this week. Biological aging is also linked to circadian misalignment because it directly affects mitochondrial function. From mtDNA leaking into the cytosol to ROS to the electron transport chain. We truly are one complexly coordinated group of systems. Much appreciation for being a paid subscriber. Thank you for your support.
Hi Kristen, any good review article on the molecular mechanisms of Circadian rhythm. I love deep dives into the molecular mechanisms and mechanistic pathways. Would like to read a comprehensive review article that soundly summarizes the full molecular mechanisms starting from the SCN master clock all the way to the peripheral clocks, including the transcriptional pathways. Thank you in advance 😊
This is something that I have put together across a few different pieces and there is already quite a bit of research available to walk through the molecular mechanisms. It is incredibly interesting physiology. For example, cells in a petri dish can keep their own time for weeks without synchronizing to the central clock in our hypothalamus. And, there are hundreds, if not, thousands of peripheral clocks throughout our body and each of them are and trained by different timing activity. Thank you for the article recommendation - look for something in your mailbox in the next couple of weeks.
I believe we are well beyond the stage of questioning whether circadian biology is “real” or clinically relevant. The mechanistic foundation is solid, and its physiological effects are consistently shown across various systems. The real challenge now is implementation. Modern medicine still largely relies on a “one-size-fits-all” approach, standardised protocols aimed at efficiency and scalability. However, circadian biology does not operate that way. Two individuals can respond very differently to the same intervention, depending on factors like timing, chronotype, environment, and behavioural context. This variability isn’t a flaw in the science it reflects the complexity of biology. To progress, we must shift from uniform strategies to genuinely personalised approaches. Such complexity is difficult to manage within current clinical frameworks, and it’s unlikely that traditional models alone can resolve it. This is where AI and data-driven methods could become crucial not to replace clinical judgment, but to enhance it. They can help interpret temporal patterns, account for individual differences, and optimise interventions in ways that are both personalised and scalable.
The question no longer is whether circadian medicine is effective; it’s whether we are prepared to develop systems capable of delivering it.
Dr. Hunter, you've articulated exactly what Part II is all about, and I couldn't agree more with your framing. The mechanistic debate is settled. What remains is the harder, messier work of building systems capable of delivering what the science already knows.
The conversations at SRBR reinforced this precisely. The field's senior leaders were not debating whether circadian biology matters. They were debating accreditation boards, reimbursement structures, training pipelines, and which clinical partnerships are most tractable at the moment. That is a very different conversation and a more hopeful one, even if the obstacles are formidable.
The other piece I'll be making a case for in Part II is a partnership that I think is underappreciated: lifestyle medicine already has the clinical infrastructure, the patient relationships, and the whole-person orientation that circadian medicine needs to reach people at scale. The science knows what to do. The question, as you put it so well, is whether we're prepared to build the systems to deliver it.
Part II drops later today. I'd genuinely love your reaction to it.
What stood out here is how strongly the field is shifting from general ideas about timing to very precise, measurable mechanisms that could eventually shape how care is actually delivered.
Yes, that is exactly what we are going for here, Dr. Siddiqui. Thank you for pointing that out! I'm really curious, coming from an educator's perspective, what gaps do you see in your practice that I might be able to help with? Is there a set of articles or frameworks that would be helpful for you?
Excellent summary of what was discussed at the SRBR conference. Circadian biology needs to be better understood by primary care physicians who often just follow guidelines based approach and never a precision based care. This is what is lacking.
Human metabolism was never adequately taught in medical school curriculum. The understanding that human metabolism is a constant 'Flux' and not static is lacking across health care practitioners.
Understanding Circadian rhythms is crucial if we have to implement Medicine 3.0, aka., Precision medicine.
Recently there were two articles published by John's Hopkins researchers on RAR....'Rest Activity Rhythms' as a biomarker of biological aging.
People who had robust RAR's had reversed their biological age on various epigenetic clocks by several years. One cohort was in healthy older adults, whose Brain MRI's revealed improved Hippocampal volumes in those who followed robust RAR patterns.
Wrist based actigraphy data was used along with blood based DNA methylation clocks. RAR is being proposed as a biomarker to monitor rate of aging by those researches at Bloomberg school of public health at John's Hopkins.
Really great feedback, thank you for sharing your perspective, Dr. Lakkaraju, and for the article recommendation on RAR, that's a new one for me! I will dive into it this week. Biological aging is also linked to circadian misalignment because it directly affects mitochondrial function. From mtDNA leaking into the cytosol to ROS to the electron transport chain. We truly are one complexly coordinated group of systems. Much appreciation for being a paid subscriber. Thank you for your support.
Hi Kristen, any good review article on the molecular mechanisms of Circadian rhythm. I love deep dives into the molecular mechanisms and mechanistic pathways. Would like to read a comprehensive review article that soundly summarizes the full molecular mechanisms starting from the SCN master clock all the way to the peripheral clocks, including the transcriptional pathways. Thank you in advance 😊
This is something that I have put together across a few different pieces and there is already quite a bit of research available to walk through the molecular mechanisms. It is incredibly interesting physiology. For example, cells in a petri dish can keep their own time for weeks without synchronizing to the central clock in our hypothalamus. And, there are hundreds, if not, thousands of peripheral clocks throughout our body and each of them are and trained by different timing activity. Thank you for the article recommendation - look for something in your mailbox in the next couple of weeks.
I believe we are well beyond the stage of questioning whether circadian biology is “real” or clinically relevant. The mechanistic foundation is solid, and its physiological effects are consistently shown across various systems. The real challenge now is implementation. Modern medicine still largely relies on a “one-size-fits-all” approach, standardised protocols aimed at efficiency and scalability. However, circadian biology does not operate that way. Two individuals can respond very differently to the same intervention, depending on factors like timing, chronotype, environment, and behavioural context. This variability isn’t a flaw in the science it reflects the complexity of biology. To progress, we must shift from uniform strategies to genuinely personalised approaches. Such complexity is difficult to manage within current clinical frameworks, and it’s unlikely that traditional models alone can resolve it. This is where AI and data-driven methods could become crucial not to replace clinical judgment, but to enhance it. They can help interpret temporal patterns, account for individual differences, and optimise interventions in ways that are both personalised and scalable.
The question no longer is whether circadian medicine is effective; it’s whether we are prepared to develop systems capable of delivering it.
Dr. Hunter, you've articulated exactly what Part II is all about, and I couldn't agree more with your framing. The mechanistic debate is settled. What remains is the harder, messier work of building systems capable of delivering what the science already knows.
The conversations at SRBR reinforced this precisely. The field's senior leaders were not debating whether circadian biology matters. They were debating accreditation boards, reimbursement structures, training pipelines, and which clinical partnerships are most tractable at the moment. That is a very different conversation and a more hopeful one, even if the obstacles are formidable.
The other piece I'll be making a case for in Part II is a partnership that I think is underappreciated: lifestyle medicine already has the clinical infrastructure, the patient relationships, and the whole-person orientation that circadian medicine needs to reach people at scale. The science knows what to do. The question, as you put it so well, is whether we're prepared to build the systems to deliver it.
Part II drops later today. I'd genuinely love your reaction to it.