The Hypoxic Foundation of Youth: Altitude’s Anti-Aging Adaptations (part 1)
Dr. Marcus Ranney
Longevity Physician to Overwhelmed High-Performers + CXOs | Best-Selling Author | Biohacker | Guinness Book of World Records’ Holder | Building Longevity Athletes | Adventurer + Explorer
TL;DR:
Picture yourself stepping off a plane in Leh (in Ladakh, India), something I have had the pleasure of doing seven times now, the gateway to the Himalayan peaks. As the cool breeze greets you, at just over 10,000 feet in altitude, so does a surprising shortness of breath–a swift reminder from nature about the thin air and reduced oxygen at this high elevation.?
For sea-level dwellers, this moment can be both awe-inspiring and a bit daunting. Every shallow breath at this point underscores the body’s urgent need to adapt to the high-altitude environment.?
High altitudes often become formidable environments for lowland dwellers to comfortably survive in. This visceral, immediate response is the body’s first step in a remarkable series of adaptations to hypoxia–where the air has less oxygen than at sea level. The thin air and scarce oxygen challenges our bodies, forcing us to undergo remarkable physiological adaptations, a theme extensively explored in the first chapter of my best selling book , ‘At The Human Edge’.?
At high elevations, each breath contains fewer oxygen molecules, prompting immediate and long-term adaptations within the body—both of which improve your longevity and overall physical health.
Longevity Lesson (Physiological Adaptations to High Altitude)
The primary driver of these adaptations is hypoxia —reduced oxygen availability—which directly affects metabolic and cardiovascular systems. Initially, the body responds with increased breathing and heart rates, eventually refining these responses over time. Red blood cell (RBC) production accelerates and improves your body’s oxygen-carrying capacity, also readying your body to extract oxygen from the blood efficiently.
Additionally, an increase in production of a hormone called erythropoietin (EPO) is stimulated by the kidney at low oxygen levels. This signals the bone marrow to multiply the production of RBCs. As a result, you’re granted better endurance and lower fatigue.?
Adaptive Mechanisms to Hypoxia and Their Longevity Implications
Here are two key mechanisms I’d like to highlight:
Hypoxia-inducible factor (HIF) pathways are pivotal in your body’s response to oxygen availability, especially at high altitudes.?
The Nobel Prize for discoveries related to hypoxia-inducible factors (HIF) was awarded in 2019. This prestigious award recognized the work of William Kaelin Jr., Sir Peter Ratcliffe, and Gregg Semenza for their discoveries on how cells sense and adapt to oxygen availability, which includes the mechanisms involving HIF pathways.
When oxygen levels drop, HIF proteins stabilize in the body and translocate to the nucleus where they induce the transcription of various genes aiding in angiogenesis, erythropoiesis (RBC production), and metabolic adaptation. These genes help fortify vascular formation to better supply tissues with oxygen.
The longevity implications of improved HIF signaling are significant. For instance:
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2. Mitochondrial Adaptations
Our body’s mitochondria (my favourite ‘M” word!!) adapt to become more efficient while consuming oxygen at high altitudes? (like a car “learning” how to burn fuel more efficiently). This is partially achieved through changes in the mitochondrial membrane potential. It also occurs through the upregulation of enzymes involved in the electron transport chain, which improves ATP synthesis under limited oxygen availability conditions.
This mitochondrial efficiency is crucial for cutting down the production of reactive oxygen species (ROS) by approx. 50% in certain conditions . The ROS are basically byproducts of cellular respiration known to propel cellular aging and damage.?
Additionally, it also:
Overall, this process reduces the period of morbidity commonly associated with advanced age.?
Genetic Foundations of High-Altitude Adaptation
Amid these physiological tales, there's an extraordinary display of human resilience and adaptation seen in the Sherpas. While trekkers and climbers from the lowlands labor breathlessly up mountain trails, Sherpas often stride past, effortlessly carrying loads that might ground others, sometimes sporting nothing more than sandals followed by casual puffs of a cigarette.
This stark contrast isn't just about willpower; it's written into their DNA.?
The Sherpas of the Himalayas and other high-altitude populations possess genes that acclimatize to elevations where oxygen levels are considerably lower than sea level. This more-than-generational exposure has led to the development of unique genetic adaptations that help them thrive in harsh weather conditions.
Hemoglobin Differences
High-altitude populations typically have unique variations in their hemoglobin, the molecule in red blood cells carrying oxygen. These variations allow their hemoglobin to release oxygen more effectively at lower atmospheric pressures. And this ensures adequate oxygen delivery to tissues despite the thin air.
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Studies have identified specific genetic mutations in Sherpas and similar people, noting an increase in their body’s performance for oxygen transport and utilisation under hypoxic conditions.
Another study calculated the arterial oxygen saturation levels of 297 Sherpas , proving they sustained effective oxygen transportation even though they possessed lower hemoglobin levels. What’s best is that their average arterial oxygen saturation was way more than that of lowland populations.
Metabolic Adaptations
Lastly, genetic adaptations also influence the metabolism of fats and carbohydrates. High-altitude residents usually show a preference for fat utilisation , leading to sustained energy release compared to quick energy bursts supplied by carbohydrates.
Note that this metabolic process is especially advantageous in ecosystems where food intake may be sporadic or predominantly from animal sources.
Mitochondrial Efficiency
Sherpas also exhibit adaptations in their mitochondrial DNA. These adaptations help multiply the efficiency of cellular factories in using oxygen to generate energy.
Even better, it lowers the oxygen quantity needed for energy production, minimizing your body’s lactate (which causes fatigue) output in the process. Another benefit is how it supports sustained physical activity without the regular fatigue experienced by lowlanders.
Comparison with Sea-Level Dwellers
Remember that individuals living at the sea level haven’t developed the above genetic adaptations because the evolutionary pressure of hypoxia is absent.
Longevity Lesson
The natural increase in antioxidant production at high altitudes can protect us against oxidative stress. If you are lucky enough to be able to consider incorporating a hiking holiday for your next vacation, that mimic high-altitude conditions. You can engage in intermittent altitude training to double down on your metabolic health and longevity.
Similarly, athletes training at high altitudes can experience large improvements in performance when they resurface to sea level. Even non-athletes can benefit from mild altitude exposure to continue improving their cardiovascular health and overall fitness.
For those who can't, then a new machine called the HBOT (Hyperbaric Oxygen Therapy) Unit can mimic some of the inducible HIF benefits. This is a technique I use in the Olympians and athletes I train but I shall leave this for another newsletter topic.
Moving on, the several physiological changes that occur in response to high altitude, such as increased erythropoietin (EPO) production and mitochondrial efficiency, continue delivering valuable for medical science and longevity. These adaptations can inform treatment strategies for low-oxygen issues like COPD and anemia.
The lessons derived from high-altitude adaptations aren’t just theoretical—they offer practical and actionable strategies to prolong our longevity through our activities.?
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1 个月Thank you Doc.