Less Sleep and a Longer Life, a Desirable Mutation

A person who sleeps six hours rather than eight hours every day, give or take, is effectively gaining a bonus 12.5% additional time spent alive and active. From that perspective, there isn't all that much difference between being able to sleep two hours less every night throughout life, without consequences, and being able to live for the better part of an additional decade in good health. There are mutations that produce this effect in humans, other mammals, and lower animals such as flies, and at least one of them does so without any apparent negative side-effects.

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.

A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila

One of the most well-studied examples of natural short sleepers in the human population are individuals with rare genetic mutations in the dec2 gene. Dec2 is a transcriptional repressor that, in mammals, is recruited to the prepro-orexin promoter and represses the expression of orexin, a neuropeptide that promotes wakefulness. A single point mutation in dec2 (dec2P384R) inhibits the ability of Dec2 to bind the prepro-orexin promoter, resulting in increased orexin expression. Consequently, wakefulness increases, and individuals sleep on average 6hrs/day instead of 8hrs/day.

Intriguingly, these natural short sleepers do not appear to exhibit any phenotypes typically associated with chronic sleep deprivation, and expression of the dec2P384R mutation in mice suppresses neurodegeneration. Thus, it has been suggested that individuals harboring the dec2P384R mutation may employ compensatory mechanisms that allow them to thrive with chronic sleep loss. However, whether the dec2P384R mutation directly confers global health benefits has not yet been tested experimentally in any system.

In this study, we used a Drosophila model to understand the role of the dec2P384R mutation on animal health and elucidate the mechanisms driving these physiological changes. We found that the expression of the mammalian dec2P384R transgene in fly sleep neurons was sufficient to mimic the short sleep phenotype observed in mammals. Remarkably, dec2P384Rmutants lived significantly longer with improved health despite sleeping less. In particular, dec2P384R mutants were more stress resistant and displayed improved mitochondrial fitness in flight muscles. Differential gene expression analyses further revealed several altered transcriptional pathways related to stress response, including detoxification and xenobiotic stress pathways, that we demonstrate collectively contribute to the increased lifespan and improved health of dec2P384R mutants.

Finally, we provide evidence that the short sleep phenotype observed in dec2P384R mutants may be a result of their improved health rather than altered core sleep programs. Taken together, our results highlight the dec2P384R mutation as a novel pro-longevity factor and suggest a link between pro-health pathways and reduced sleep pressure.


I want this...

Posted by: Corbin at May 24th, 2023 3:03 PM

I'd rather live longer so that I can get over that life extension finish line.

Posted by: Matt at May 24th, 2023 6:22 PM

Hi there! Just a 2 cents.

I would be careful (extrapolating), study results; some animals function with less sleep/intermitent sleep/chunked sleep (waking up/going to sleep - several times, in a single night), others not so;
interrupted sleep = acceleration of aging; you may get all your hours, even with broken sleep;

In the other sleep studies it showed that it was not so much, interrupted sleep the problem; it was lackthereof; as you age you may experience insomnia, not sleeping enough hours, and broken sleep/repeatedly/interrupted sleep; and that can be highly deleterious over long run.

When sleep is broken, it 'breaks the circadian clock'....rhythm. 'day-night, day-night, da...' cycle.
Which is genetic (circadian clock). The clock will have to adjust/readjust to these sleep pattern disturbances...

It was shown that when you lack sleep you increase 'all cause mortality', rapidly, and can even die of 'sudden death' -- in young age (worse, in old age). I don't remember but it could be up to 2-times increase in all-causes...meaning, it's as if you started smoking 6 packs of cigarettes a day....like, it equalled the risks that come with long smoking, obesity, junk food, no exercise, stress, depression, sedentarity...

It's true, sleeping 2 hours less; like a house-fly (proportionnaly), will give you 'more time awaken/awake....living/doing/being......instead of 'in sleep/sleeping''. And, yes, that's roughly a 10 years extra of life, 'awoken'...instead of asleep.

But, that's the thing, you may get 10 years extra -- because you are 2 hours less in sleep time...
for just 6 hours of sleep...

- but, you will not 'reach'....that age--- to get that extra 10 years.

I.e. you will die Before..that. As in, the fact that you will sleep less - will Accelerate your demise and accelerate your death. You could, very well, die 10 or more years; earlier, due to not sleeping enough hours.

6 hours is not enough; it is dangerous to say so (also); people that sleep 6 hours per night...
are, effectively, digging a faster ground hole/grave (for them).

It was shown that there is a 'goldi-locks' zone....between 6 and 8 hours...and that's, Seven flush.

7 hours is the gold 'mean'; below that mortality rises...above that, mortality rises - Too.

8 hours of sleep it starting to be too much and can actually make a languishing/dysfunctional sleep; where the person Still wants to sleep More....yet, they already slept (enough) 8 hours...
Now, some times, you Need 8-9...hours...heck, even 10-12...13 hours..like a child. Children and babies, can sleep up to 15 hours....some times, even adults, need 'repair/repairing sleep' that goes Above 7 hours; that is just - some, times, when weak, severely tired, damaged and frail...not the regular/routine sleep'.

For adults, that is deleterious - above 7. 8 is already too much.
It was shown that there could be problems with above 8 hours; like sleep ischemia/sleep apnea', you start to lack oxygen in your sleep; or your flesh membranes can 'obstruct' oxygen flow...this can cause brain pruning -- ischemia by lacking of O2; so sleep is not suppose to go on forever, nor it is suppose to be less than 7 hours (for adults).

Aim for 7 hours, and you will have the better health; it was striking that Even - just - 30 minutes less has an impact; Sleeping 6 hours and a half....is deleterious...you suppose to get Full 7 hours.

The reason why, is because the Whole Sleep Process...basically, is best, in 7 hours...
REM (Rapid Eye Movement), Deep Sleep...and the several 'phases' of sleep; when the body triggers 'HGH' (human growth hormones) to repair the tissues and also, while in sleep, 'neuron recalibration/neuronal firing' -- like pistons of an engine...testing the spark plugs and the motion..
The pineal/glands will produce the hormones (of course, melatonin to fall asleep) but also, the ones to make 'growth' so that the next morning; you have renewed tissues/repaired bodily damage/tissues. It's why they say: ''Sleep is thy medicine; it heals/repairs thyself''.
You need deep sleep (uninterrupted), at the 'right amount' of hours (7). And, you must 'dream/REM'. During dream, is when it 'happens'/brain doing its thing...many microvesicular and astrocytes/monocytes will 'remove the crap'/brain clean...same, for amyloids/tau/aggregates...

Lack sleep --> accelerate death/accelerate 'brain pruning/brain gray/white volume matter loss' --> acceleration of diabetes, parkinson's, dementia, mental fog/slowness, depression, alzheimer's...

So, no, don't sleep 6 hours, unless you wish accelerated death/wish. You must Give Enough time for your body to heal/repair...and that means, a long enough, sleep; and not more than that. That, means, seven hours (bell shape/u-curve graphic for adult mortality; 6 or less = death; 8 or more = death). That leaves seven, in the middle/average.

1 hour less,(to sleep only 6) is not worth the dramatic risk increase of death....just 1 (Whole) Hour less..will increase your death risks..

It was shown that Centenarians/Supercentenarians -- have Monotonic sleep patterns...-they sleep Exact same number hours -- For Decades. They never change their sleeping patters...
always 7 hours....Sleeping at 12:00 AM --- in the bed...they do stay up one more minute. They fall to sleep -- in less than 5 minutes. They are 'early birds' (not noctural birds)...they wake up at 7 am.

Good Sleep, Long enough Sleep = Repair/Correct Circadian Clock (trained)/correct genetic sleep patterns) = Longer Life.

It is simply too dangerous to skip 1 hour of sleep (6-), or, sleep 1 hour too many (8+).
What works in a fly (less sleep, long life/more 'time spent up/awaken'..than sleeping) does not, necessarily, translate (well) to humans. Or, at all. Humans, need Much More Repair...during their sleep...than a fly...hence, need the sleep.

Thanks for reading,
Just a 2 cents.

PS: You can sleep less, it's just you taking your chances....I remember a young time, my mom would tell me at night, with me staying up late : ''Gooo to Sleep...now!''....she was right all along.

Posted by: CANanonymity at May 24th, 2023 11:35 PM

PPS: The circadian clock is - intimately - connected/linked to the Epigenetic clock.
Disturbed Circadian Clock (Chronically) --> Disturbed Epigenetic clock/Disturbed Chromosomal function --> Epiclock Acceleration --> Accelerated Aging.

Circadian clock = sleep genes = part of epiclock, that regulated genes; or, sleep genes/patterns.
Circadian clock = Epiclock. (epicircadian clock).
When circadian clock was continously disturbed -- there was clear epigenetic consequences (some Irreversible/Permanent) and epichanges in teh epiclock/epimethylome...all this means, again, accelerated (clock) aging.

It was demonstrated taht people that can suffer of mental diseases, depression, slow mind, forgetful mind (alzheimer's/amnesia)...they showed distiurbe/accelerated epigenetic clock/age.
Especially (evidently) in the brain...your brain Needs your sleep, so much.

Posted by: CANanonymity at May 24th, 2023 11:54 PM

Less sleep and not wasting life with unproductive exercise is for now the only proven life-extensiion.

Posted by: Jones at May 25th, 2023 12:15 AM

''We reported a mutation in the human DEC2 gene that causes mutation carriers to sleep 6 hours nightly for their entire lives without apparent negative effects. Another mutation in DEC2 was later reported in a single individual who is a short sleeper and resistant to sleep deprivation. Identification of additional genes participating in modulation of human sleep duration provides a unique way to expand our knowledge of genes and pathways critical for human sleep homeostasis regulation.''

''We report here a rare mutation in the β1AR gene (ADRB1) found in humans with natural short sleep. Engineering the human mutation into mice resulted in a sleep phenotype similar to that seen in familial natural short sleepers. We show that β1AR is expressed at high levels in the dorsal pons (DP). Neuronal activity measured by calcium imaging in this region demonstrated that ADRB1+ neurons in DP are wake and REM sleep active. Manipulating the activity of these ADRB1+ neurons changes sleep/wake patterns.''

I guess, some humans, do have this natural ability to sleep only 6 hours and it works fine (it is definitely not my case);

I would wager they are in the small number and are not the large contingent with this mutation. They do say, ''a rare mutation in the β1AR gene (ADRB1) found in humans with natural short sleep''.

So, I guess (again), it can work....but, the thing is....what says you have this mutation; what says you can 'count' on sleeping only 6 hours or less.....if you feel fine; then...I guess, Ok.
But, for many people, it's just not enough and thus, they do not have this mutation.
This is a special CNS (Central Nerve System/Neural System) and specific neurons (ADRB1+ neurons)...mutation; that, in this case, is beneficial - despite, sleeping less. As they, say, there is complex interplay between noreadrenaline, CNS, and neurons; and sleep. Because, adrenaline and noreadrenaline...are what 'wake you up'...when you wake up. As they, also, say; the beneficial advantage would be that these neurons are protected and are beneficial to the Overall Health; which, in turn, should have positive effect on the circadian clock/and epiclock.
If health is preserved, it will show in circadian/epiclock, in some aspects (albeit, (some aspects) of, health and aging, can be disconnected/uncoupled, even if related/dependent; even, in the clocks).

It is better (I think) to play it safe...and just believe you don'T have this rare advantageous mutation; and sleep (a bit) ..more; than less. There is a drastic mortality increase in many people when below 6 hours. It's clear, in their case, they don,T ahve this sleep-deprivation 'but compensation' mutation that compensates for less sleep.

You can sleep less, just try stopping at the minimum of 7. If you want to believe you ahve the mutation....you take your chances..with 6 or less (so long, as your body can take it).

Posted by: CANanonymity at May 25th, 2023 12:35 AM

I would like to have a gene that reduces facial hair growth or growth of hair at head. You save time by not having to cut it often. You've likely seen the ad which sows an average man cuts 2 soccer fields annually with facial hair. Women are more luckier there.

Posted by: ciclo at May 25th, 2023 10:10 AM

Sleeping fewer hours without worsening health is not a real life EXTENSION

It is a subjective improvement of quality of life. Sleep without dreams may be considered
a waste of time, providing that those sleepless hours are spent meaningfully and purposefully.

There are other methods to improve quality of life:
* not being drunk or intoxicated
*not being religious and not spending time in religious activities
*not taking vacations
*not being married and not spending time in marital disputes, arguments
* not being poor and not spending time working in unpleasant jobs

But reading anti-AGEing blogs and literature is not a waste of time - it is time spent meaningfully.
It is all quite subjective: what is a waste of time for one person - may be quality time for another person.

Posted by: Nicholas d. at May 25th, 2023 2:58 PM

@Nicholas, the interesting thing about this study is that not only did the flies sleep less, they *also* had a longer lifespan, by a pretty significant margin. If the goal is to reach LEV then getting more hours in your day from sleeping less doesn't help much (unless you are a researcher that can cause LEV to happen sooner with those extra hours). However, if this translates to humans then you get both the extra hours in the day *and* extra years on the end.

Posted by: Micah Zoltu at May 27th, 2023 11:16 PM
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