Where do the extra several years come from …well there are a few people who have a gene mutation that means they sleep 1-2 hours less than everyone else.
My wife once asked me if there was one thing I could change about myself, what would it be and I said “Yes, i’d like a DEC2 gene mutation please" ……she didn’t get it.
Not only do they have a ‘driven’ personality, they have more energy, appear immune to jet lag, may have a resistance to Alzheimer’s, and may actually live longer.
Yes, I have read about this. Seems like it could be a pretty simple gene therapy!
I am not much of a morning person. I would love this.
Yes, I think I read it was only a single point mutation, and the geneticist said it would be quite easy to do. Even better if we could do it pharmacologically.
I used phenelzine once to achieve a similar effect, used it to completely suppress my REM sleep, I literally bounced out of bed ready to go at 5am. I need to stay pretty alert for about 4 days with very little sleep and perform a complicated procedure at the end. Only used it for a short period as it got a bit weird.
What does the gene affect? For example, intelligence genes I imagine form the brain early life, so it’s not possible to enhance it by switching them on later. Is the same thing with this gene?
DEC2 helps control levels of orexin, a hormone involved in maintaining wakefulness. (The sleep disorder narcolepsy is caused by too little of this hormone.) The mutation in DEC2 seems to work by partially releasing the breaks on orexin production.
It is suggested that DEC2 may lower your level of alertness in the evening by binding to and inhibiting MyoD1, a gene that turns on orexin production. Before dawn, DEC2 fades away, allowing MyoD1 to stimulate orexin production to wake you up and keep you alert throughout the day.
The mutation seen in human short sleepers weakens DEC2’s ability to put the breaks on MyoD1, leading to more orexin production and causing the short sleepers to stay awake longer.
My orexin has kicked in, it’s 2am and time for bed 
It’s every over-achiever’s dream: a gene mutation that allows them to function normally with just four to six hours of sleep a night instead of the normal eight.
In 2009, UC San Francisco neurology professor Ying-Hui Fu, PhD, discovered a mutation in the gene DEC2 in a family of natural short sleepers – people who go to bed at a normal time (11 p.m. to midnight) but wake up naturally at 5 in the morning. “These are not people who’ve trained themselves to wake up early. They’re born this way,” says Fu.
A new study in mice by Fu’s lab – published in PNAS on March 12, 2018 – reveals how the DEC2 mutation seen in human short-sleepers may allow them to survive and thrive on just a few hours of sleep.
@Guywholikessleep - I’m sure you’re knowledgeable about this mutation… any new and additional information you can share? What do you think, would it be a good gene mutation (or group of mutations) to get via a little gene therapy, to make give ourselves an extra 20% effectively longer day, and lower risk of Alz/dementia?
This seems like another potential product / service for the guys at Minicircle Roatan: https://minicircle.io
And, people’s experiences with having this gene mutation - a fun story:
By 2009, the team published their first finding: There was a mutation in the gene DEC2 which caused short sleepers to stay awake longer. Since then, the team has discovered two more genes – an ADRB1 mutation and a NPSR1 mutation – which alter neurotransmitters in the human brain to create short sleep.
and some videos on the topic:
Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41 ) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin , also known as hypocretin (Hcrt ), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R ). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc ) expression through cis -acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.
Expression of human dec2 P384R in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2 P384R mutants lived significantly longer with improved health despite sleeping less.
Do short sleepers live longer?
A recent study on the genes that promote short sleep found that people who are natural short sleepers reap several benefits of sleeping fewer hours per day — including living longer.
Your short sleep duration may also be responsible for:
What is Short Sleep Syndrome? | LifeMD.
After 10-Year Search, Scientists Find Second ‘Short Sleep’ Gene
https://www.cell.com/neuron/fulltext/S0896-6273(19)30652-X
I’m not really seeing longevity in humans…
Which is also consistent with this:
Today’s open access paper offers an exploration of one of these mutations, a small alteration in DEC2, which not only reduces the need for sleep, thereby granting additional subjective life span, but is also found to extend actual life span in flies. The size of the effect is larger than many of the calorie restriction mimetic compounds explored in recent years. Interestingly, the authors here argue that reduced need for sleep is more a reflection of increased robustness and health resulting from this mutation than any independent, top-down alteration of the regulation of sleep.
Or has anyone seen anything in humans / or MR studies on these two genes?
Lets talk about Dec2 and orexin.
Dec2 is essentially involved in Circadian rhythm regulation at the molecular level known as the transcriptional feedback loop. This loop essentially helps with the synchronization of the circadian rhythm with whatever cue (light, food, etc). At the core is a molecular feedback loop in which the proteins brain and muscle ARNT-like 1 (BMAL1; also known as ARNTL) and CLOCK act as transcriptional regulators and drive the expression of the period homologue 1 (PER1), PER2, PER3 and cryptochrome 1 (CRY1) and CRY2 genes. A complex that is formed by PER1, PER2, PER3, CRY1 and CRY2 proteins enters the nucleus and then impedes the BMAL1 and CLOCK-mediated transcriptional drive. The complex therefore acts as a transcriptional repressor of its own genes. DEC2 is part of a transcription regulation process where they function similar to Per1 AND Cry 1, where they can repress transcription of BMAL/CLOCK.
Circadian rhythms play a role in timing and synchronization of some process to some cue. In diurnal creatures their circadian clock synchronizes where light = awake/activity processes and night=sleep/rest processes. There are many other processes that the circadian rhythm impacts. It can influence many other organs and activity, sleep is just one of those processes but not the only.
There are contrasting thoughts on the circadian rhythms influence sleep.
There are multiple schools of thoughts and a lot of debate of circadian rhythms influence on sleep. I personally don’t think any of them are right at the moment, since it’s hard to separate the interaction between sleep and circadian processes completely.
There is the two process model, where Process C(circadian rhythms) controls the TIMING of sleep/wake, and process S is the sleep pressure accumulation throughout wake that DRIVES SLEEP NEED.
I think this model is the most accurate in terms of evidence, but there are exceptions to this model.
There is also the opponent process model where there is a competition between Process C and Process S. In this model , Process C drives us awake. Process S accumulates during wake, competing with Process C to control the behavior of the organism. Process C stays high throughout the day but then dips around 2-3pm jn the day. In this time period Process S would be high and could potential result in sleep. This period is where Nap would potentially occur. The Process C drive then promotes wake again, and process S accumulates. At bed time, Process S over takes Process C , resulting in sleep where both Process S and Process C drive decreases and repeats the next day.
Evidence for this model is lacking in terms of credible studies so most people stick with the two process model.
Regardless, there are examples that can be exceptions to the processes such as mutations in clock genes resulting in changes in sleep timing/pressure(PER3, CLOCK, BMAL1,etc). There are also examples where disruption of circadian genes has no influence on sleep timing or pressure. The consensus is mixed that I find neither model to be all encompassing now.
If we look at DEC2 by itself, it plays a important role in circadian rhythms but other proteins can take its role. Mutations in DEC2 cause short sleep syndrome, but it’s hard to discern its exact role in the mechanism or if its having a direct influence on sleep directly or other processes that may influence sleep. An example could be orexin.
Orexin is a neurotransmitter that is a part of the ascending arousal system(wake promoting system) of the brain circuitry that promotes sleep. Orexin is thought of as a “switch” that changes the behavior of the brain circuitry to either activate and stabilize wake, or shut off the arousal system. Orexin is released from the Lateral hypothalamus and drives to activate the ascending arousal system and stabilize its activation. A region that is responsible for promoting sleep is the Ventral Lateral Preoptic Nucleus(VLPO) and serves as a place where inhibitory signals are sent to wake promoting regions, initiating sleep. Orexin will inhibit regions involved in sleep and REM from activating. In Narcolepsy orexin is lost which is why those individuals enter REM sleep or enter sleep randomly.
The idea essentially is that orexin controls the transition state between wake and sleep. There is controversy in this idea of orexin, but that is one plausible school of thought.
The issue becomes in that orexin and VLPO neurons have mutual projections, but VLPO lack orexin receptors. Orexin seems to reinforce arousal system properties but does not directly inhibit the VLPO. One interesting fact about sleep is that you can lesion any of this brain circuitry involved and have sleep still occur. This fact alone is why I think that all these brain circuitry and processes are just a part of the nature of sleep and are just areas that act in certain ways during sleep but do not govern it sleep completely. Also too, orexin may be playing another role we have yet to distinguish in the whole sleep-wake biology. Look at the VLPO. VLPO has GABAergic neurons that inhibit wake promoting circuitry, but recent evidence has found there are different GABA receptors in the VLPO and they do contrasting things.
Although DEC2 results in short sleeper syndrome, it is very rare. Also, DEC2 seems to play a role in sleep, but is it directly or through other influences (i.e changing other organ behavior that influences sleep/wake, involved in some separate biological process that somehow alters sleep )? There have been examples of Clock Genes that can alter sleep but not be located in the brain(in whole body Bmal1 KO, restoring Bmal1 expression in the brains of Bmal1- knockout mice did not rescue Bmal1-dependent sleep phenotypes. Surprisingly, most sleep- amount, but not sleep-timing, phenotypes could be reproduced or rescued by knocking out or restoring BMAL1 exclusively in skeletal muscle) so is everything acting in the brain or other tissues? Same can be said about orexin.
The increase in hypocretin proteins suggest to me that the benefits are not with shortening sleep, but something to do with either the decreased need for sleep or something involved with another process. The author’s even state “that reduced need for sleep is more a reflection of increased robustness and health resulting from this mutation than any independent, top-down alteration of the regulation of sleep”. Also, what other effects might this mutation cause?
There is SIGNIFICANT studies showing that sleep deprivation or not getting normal sleep is detrimental and that changes to circadian rhythmicity is also detrimental (Shift work is a good example).
I think more information needs to be gathered. We don’t really know the exact role orexin plays in sleep or DEC2’s mechanism of action. DEC2 may be a target of interest but also may not be having benefits in altering sleep and acting through some other property.
Thanks for the great and in-depth response. Its always good to hear from someone who deeply understands a subject as my tendency (likely a general human trait, especially in biohackers) is to oversimplify and say “Hey, we should do that gene alteration in humans via gene therapy so we can get the same results” 
But, I have to believe someone out there in a lab is now doing the “Knock-in” of that DEC2 / Orexin mutation in mice to learn more about how it works.
When I was in college, I had a friend who only needed 4 hours of sleep a night. I needed 8.5. I remember figuring out that he would be awake something like 7 more years than I would by the time we were 65. I tried to emulate his schedule and it went bad pretty fast.
