|The Mother of All Clinical Trials, which I announced in April, continues to progress at a charmed pace. This is a project to collect information from people who are already using a variety of measures to extend their life expectancy, and to use a methylation clock and some innovative statistics to tell us which combinations are effective. It is to be an open-source study, with all data, results and analysis freely available to the public and the research community.We have done no fundrasing as yet, but have collected remarkable volunteer talent and a mammoth donation-in-kind from Zymo Research, the only company that presently offers methylation age testing commercially.
Our principal unfilled role is a project director, who will recruit, train and manage 5,000 subjects from within the life extension community, oversee collection of data, and keep them motivated. This could be a volunteer position, or it may involve fundraising your salaray + related expenses.
We are also looking for a lawyer who can advise us on privacy, HIPAA, IRB matters, and related IP issues. Write to Josh Mitteldorf <email@example.com> if you are interested in working with us.</firstname.lastname@example.org>
My Himalayan Experience
I’m going to invoke my prerogative as a blogger and talk a bit about my personal experience. Two weeks ago, I was trekking in the Himalayas. This adventure has been on my bucket list for many years, both because of the grandeur of the landscape and the challenge of exercise at high altitudes. This spring, I finally got around to it.
On the rare occasions when I’ve been above 4,000 meters in the past, I was a little short of breath but didn’t have headaches or nausea that are commonly experienced. A week before my trip, I looked up the Chinese word for altitude sickness and stopped into the herbal pharmacy at the shopping mall near where I was living in Beijing. The pharmacist offered a box of pills, whose ingredients included rhodiola, Goji berry, ginseng and taurine, all of which have some evidence as longevity aids.
I arrived at Lhasa airport at 7 in the evening (3600 meters) but the sun was still high in the sky, due partially to the fact that it was close to summer solstice, but mostly because China’s single time zone should really be 3, and Tibet is in the far west. I had a limo to the city, and didn’t feel bad at all. I went out for a late dinner, and felt the first headache symptoms as I went to bed. In the middle of the night I awoke with a rip-roaring headache, and a sense of déjà vu. Only then did it dawn on me that I had forgotten to ask the waiter at my restaurant to avoid MSG in my meal, a mistake which I had already made twice before in my 8 weeks in Beijing. The headache was gone by mid-morning, and never returned during my week in the Himalayas.
For the trek, I was tacked onto a group from Singapore, all half my age. We were out at 4,000 to 5,000 meters over four days, covering about 20 Km per day of ups and downs. Air at 5,000 meters is just about half the pressure (half the O2) compared to sea level. I never felt sick, but I was out of breath whenever we walked uphill, even a small incline. For the second day out when we first crossed 5,000 meters, I was doing kapalabhati for hours on end (fast, yogic belly breath) — pumping air into my lungs as fast as I could to avoid the lightheadedness that would stop me in my treks.
Apnea – the mind cure
I have had sleep apnea for 20 years. When I’m asleep, my body forgets to breathe, until my brain senses oxygen deprivation, startles me half-awake, I gasp a few breaths, fall back asleep, and the same cycle repeats. I’ve just barely managed the condition by sleeping on my stomach. Sometimes I’m aware of the apnea as it happens, but mostly I’m not; during the day I have bouts of sleepiness, presumably because my nighttime sleep is not deep, and I’m fortunate that usually I have the freedom to take naps as needed.
What I didn’t learn until I got to Lhasa: Altitude makes apnea worse. On the one hand, there’s less oxygen, so we need to be breathing faster; on the other hand, there’s also less CO2, and it’s the buildup of CO2 in the blood that the body senses in order to regulate breathing. I usually take 1 mg melatonin at bedtime, for longevity benefit rather than for sleep. While in Tibet, I suspended melatonin because statistically it exacerbates apnea, and in my experience, melatonin at higher doses seemed to be a major factor.
My first night out on the trail, I really sensed the apnea, much more so than in Lhasa. I repeatedly felt myself startled awake, panicked and panting. I wasn’t sleeping much.
The second night, my difficulty sleeping was more severe, and I was inspired in the middle of the night to try an experiment. I sat erect in a meditation pose and found a rhythm that gave me enough air = 3 heartbeats inhale, 5 heartbeats exhale. (This was about three times faster than my resting breath at home.) I used meditation techniques to keep my mind returning to the breath, aware of the rhythm, and aware when the O2 budget felt insufficient, and I needed to breathe deeper and faster for a bit. After about 20 minutes, I lay down and maintained the same counts, the same breathing rhythm, the same relaxed, meditative mental posture. I deliberately formed the intention to impress the rhythm on my unconscious, so that it might continue to breathe in the same pattern after I dozed off. The technique worked. It was awhile before I dozed off, but the time meditating was fully relaxing, and gave me the feeling that my brain and body were restoring as they might have if asleep. When, eventually, I did fall off to sleep, there was no panicked awakening. I can’t be sure whether the apnea was returning because I was in a tent alone, but as far as I could tell, it was relaxing sleep.
I regard the experience as a breakthrough in my relationship with apnea, and I’ve continued to rhythmically breathe myself to sleep in the 2 weeks since I’ve returned to sea level.
Adaptation to Altitude
Many peoples around the world who are adapted to high altitude living have more red blood cells. This works to carry more oxygen more efficiently to the tissues, but high RBC inclines the blood to clotting, and increases risk of heart disease and stroke. The Himalayan peoples have a better idea. They actually have lower RBC counts than the rest of us, but they have a genetic variant known as EPAS1 that enable their mitochondria to function just fine, to burn sugar efficiently at low oxygen levels.
Until recently, the origin of EPAS1 was a mystery. Then, in 2014, the geneticists traced it to a group called the Denisovans, 40,000 years ago. Denisovans were an offshoot of Neanderthal man, chronicled from a single finger bone of a single young woman, found in a cave in Siberia in 2010. The bone had enough DNA to do a complete sequence, and an entire subspecies known fro this single example. The Denisovans interbred with other human tribes of Asia, and the EPAS1 gene was originally their contribution to humanity. It disappeared in many places, but in Tibet, it was useful, so it stuck.
It may be counterintuitive that more is not better when it comes to red blood cells. P.D. Mangan has been beating the drum to advise us that iron levels on the low side of normal are better not just for cardiovascular risk, but for many other aspects of health as well.
Benefits of Hypoxia
Tibetans have short life expectancy compared to other Chinese groups. This may be due to poverty and inadequate access to medical care. But, curiously, there is also a high concentration of nonagenarians and centennarians in Tibet. Could altitude be a factor?
There is indirect evidence linking hypoxia to longevity. Hypoxia shifts gene expression toward a stress response that is known to overlap with longevity genes [ref, ref]. Hypoxia increases lifespan in bees [ref], fruitflies [ref], and lab worms [ref]. A study correlating altitude with life expectancy across the US found tentative evidence for a benefit from living at higher altitude.
I’m not impressed by the arguments that hypoxia is a factor in the longevity of whales, naked mole rats, and other animals whose lifestyles incidentally lead to hypoxia–too many confounding variables.
Evidence on apnea
Apnea is two separate diseases. Obstructive Sleep Apnea (OSA) has a mechanical origin in blockage of the windpipe. It is associated with obesity, but studies find that independent of obesity, apnea is a mortality risk. Central Sleep Apnea (CSA) originates in the central nervous system, but its logic and mechanisms remain obscure.
OSA incidence increases modestly with age. CSA increases dramatically with age.
(from a Korean study 2018)
CSA is much rarer than OSA, but its incidence increases dramatically after age 65. (For CSA, I was unable to find a graph like the above.) CSA is associated with heart disease and stroke, and the direction of causality is unclear. It may be both that heart failure contributes to apnea and apnea contributes to heart failure [ref]. For those of us who suffer from CSA, it would be interesting to know if treating the symptoms (say, with CPAP) lowers cardiovascular risk. Consensus of the medical community is “yes”, but this conclusion may be driven by economic and legal factors. I have been unable to find a definitive answer in the primary literature, because the direction of causality is so hard to discern. This small study (2005) found a major decrease in 5-year CV mortality for those who accepted CPAP treatment compared to those who could not tolerate CPAP. This larger study (2016) found that CPAP effectively alleviated the symptoms of apnea, but had no discernible effect on CV mortality. Of course, better sleep at night and better alertness during the day are sufficient reasons to treat the symptoms of apnea. But some of us aren’t helped by CPAP.
The Bottom Line
Hiking at high altitudes is a great challenge, but not necessarily the best conditioning for long life. Unless you’ve got Denisovan genes, you will adapt with higher red blood counts, which, for most of us, is a net negative.
Sleep apnea is entwined with heart disease, so it is difficult to separate cause and effect. Lowering the risk factors for apnea may be as important as treating the apnea itself. There is but little indication that sleep quality directly affects your mortality risk, but it certainly affects quality of life.
From what I have seen, there is a well-established correlation between apnea and increased mortality, especially CV mortality, but it is not clear that apnea patients using CPAP have lower mortality than untreated apnea patients. I’m taking a controversial position based on 2 days’ reading, and I could be very wrong about this, so I invite response and discussion.
My own experience suggests that it’s possible to use meditation techniques to plant suggestions in the unconscious that alleviate sleep apnea and improve sleep quality. Hypnotism, autosuggestion, and biofeedback might be effective as well. It’s hard to do controlled studies to demonstrate this benefit, and it may be even harder to get them funded. But it’s an approach worth exploring.