Aging is a natural process that every living organism undergoes, and while it's an inevitable part of life, scientists have long been intrigued by its underlying mechanisms. As we evolve, so does our science, and we as human beings strive to take upon research questions that have defined humans since the beginning of time, one being immortality or to the least delaying death.
Co-founder of Pay-Pal, Peter Thiel invested $3.5 million in a foundation said to work on the “problem of mortality” back in 2006. Since then, many such search works have been in play that work towards increasing the human lifespan.
Scientists have long thought that ageing could be caused by molecular damage that accumulates in our bodies over the course of time. The damage is an unavoidable by-product of breathing oxygen, the very element that keeps us alive, and other metabolic processes that are necessary to life.
In a recent research finding published by the Harvard Medical School on May 23, 2023, we find that mice that were deprived of oxygen, roughly equivalent to a Mount Everest base camp, actually lived 50% longer than expected.
In this blog, we will explore the complex relationship between oxygen and ageing, shedding light on both its benefits and potential drawbacks.
The Oxygen Paradox
Oxygen is essential for life as we know it. Our cells rely on this vital molecule to produce energy through a process called cellular respiration. It's the reason we breathe, as our lungs extract oxygen from the air and transport it to cells throughout our bodies. Without oxygen, life as we know it would cease to exist.
However, there's a paradoxical side to oxygen. While it is indispensable for energy production, it can also cause harm in the form of oxidative stress. Oxygen molecules, particularly reactive oxygen species (ROS), can damage cells and their components, including DNA, proteins, and lipids. This damage can accumulate over time and is often implicated in the ageing process.
Some studies have shown that oxygen limitation (limiting the oxygen content of the air to well below sea level, about 21 percent) can also extend the life of a variety of models, including fruit flies, worms, yeast, and mammalian cells in laboratory dishes. However, until now, oxygen limitation during mammalian ageing has remained unexplored.
To test this idea, Mootha, Rogers and their colleagues (at Harvard Medical School) worked with prematurely ageing mice. These animals die of age-related diseases at about 3-4 months of age, compared to normal, or "wild" mice, which live for about two years.
The results of this experiment were nothing short of remarkable. Mice living in the hypoxic chamber exhibited significant increases in both median and maximum lifespan. On average, they lived approximately 50 percent longer than their counterparts exposed to normal oxygen levels. The maximum lifespan of these mice increased by about 30 percent.
Beyond the extension of life, the researchers observed another intriguing phenomenon. Mice residing in the oxygen-restricted environment demonstrated preserved neurological function for a more extended period. Their coordination and strength, as measured by standard tests, remained superior compared to their counterparts living under normal oxygen concentrations.
Future Endeavours
Despite these promising findings, the exact mechanisms responsible for the life-extending effects of oxygen restriction remain elusive. Initial investigations into potential causes, such as reduced food intake or unusual gene activity, did not provide definitive answers. This leaves scientists with tantalizing clues and a multitude of questions.
Future research endeavours will likely explore whether oxygen restriction can similarly extend the lifespan of "wild-type" mice, which do not possess the accelerated ageing characteristics of the mice in this study. Researchers will also aim to unravel the precise biological mechanisms underlying the effects of restricted oxygen and determine whether these mechanisms affect all organs uniformly.
An alternative to Oxygen as a from of Anti-Aging?
The concept of using alternatives to oxygen as a form of anti-ageing is a fascinating area of scientific inquiry. Still, it's important to clarify that oxygen is essential for life as we know it. Oxygen plays a central role in the process of cellular respiration, where it helps produce the energy necessary for cell function. Depriving the body of oxygen entirely would not be a viable approach to anti-ageing, as it would result in severe harm or death.
However, there are several related areas of research and alternative strategies that scientists are exploring in the context of ageing and health:
1. Hypoxia and Oxygen Modulation:
As discussed in the previous section of the blog, some studies have explored the effects of oxygen restriction, or hypoxia, on various organisms, including mice. The research has shown that reducing oxygen levels below those typically found at sea level can extend lifespan and improve certain aspects of health. Hypoxia chambers and techniques that modulate oxygen levels in a controlled manner are being studied for potential health benefits.
2. Intermittent Hypoxia:
Rather than continuous oxygen restriction, intermittent hypoxia involves cycling between lower and higher oxygen levels. This approach is being investigated for its potential to stimulate beneficial physiological responses, including the activation of cellular repair mechanisms.
3. Mimetics and Compounds:
Scientists are also researching molecules and compounds that can mimic some of the effects of oxygen restriction without actually reducing oxygen levels. These "mimetics" can activate specific pathways in cells associated with longevity and cellular repair. Resveratrol and NAD+ boosters like NMN and NR are examples of such compounds.
4. Oxygen Therapies:
Certain oxygen therapies, like hyperbaric oxygen therapy (HBOT), involve exposing the body to increased oxygen levels under pressure. While HBOT has primarily been used for medical purposes such as wound healing, some research explores its potential as an anti-ageing intervention.
It's important to note that research in these areas is ongoing, and many questions remain unanswered. Additionally, what works in animal models may not necessarily translate to the same effects in humans. Human biology is complex, and ageing is influenced by a multitude of factors.
Conclusion
Oxygen is undeniably the breath of life, sustaining us from the moment we are born until our final exhale. However, its dual nature as both a life-sustaining element and a potential source of cellular damage underscores the complexity of its role in the ageing process.
Understanding the delicate balance between oxygen's benefits and its potential harm is a key aspect of ageing gracefully and maintaining good health as we grow older. By adopting a balanced lifestyle that includes a healthy diet rich in antioxidants, regular exercise, and stress management, we can harness the power of oxygen to support our well-being throughout the ageing journey. While we may not be able to stop the clock entirely, we can certainly make the most of the breath of life we've been given.
References
- Decrease Oxygen to Boost Longevity? (2023, May 23). Harvard Medical School. https://hms.harvard.edu/news/decrease-oxygen-boost-longevity
- Van Vliet, T., Casciaro, F., & Demaria, M. (2021, May 1). To breathe or not to breathe: Understanding how oxygen sensing contributes to age-related phenotypes. Ageing Research Reviews; Elsevier BV. https://doi.org/10.1016/j.arr.2021.101267
- Khedkar, S. (2023, June 19). Get less oxygen, live longer? It’s true in ageing mice. The Hindu. https://www.thehindu.com/sci-tech/science/continuous-hypoxia-mice-longevity-mootha/article66982731.ece
- Staff, W. (2006, September 18). PayPal Founder Wants to Live Forever. WIRED. https://www.wired.com/2006/09/paypal-founder-/
- Gorman, C. (2013, January 30). Ask the Experts: Can Aging Be Controlled? Scientific American. https://www.scientificamerican.com/article/aging-ask-the-experts-can-aging-be-controlled/#:~:text=Scientists%20have%20long%20thought%20that,that%20are%20necessary%20to%20life.
Author
Ms. Palak Bafna (B.Tech. - Medical)