Proper sleep, a complete diet, minimizing stress (I'm personally biased towards meditation), intermittent fasting, and vigorous cardiovascular exercise complemented by strength training will by far have the most impact in maximizing your natural lifespan.
You shouldn't look at doing anything else until you've at minimum mastered all of the listed items above. Nothing else will have as much outsized impact.
This post is poorly researched or misguided relative to the topic at hand.
We are discussing drugs(or other systemic measures or therapies) that make people younger. The only thing that you can manage to do if you do all those things you listed perfectly is to come close to your theoretical maximum lifespan that is already preset in your biology/genetics. What we are trying to do with these drugs is to increase that biological span, the base span that you are currently always limited at, regardless of how many broccoli you eat or how many steps you make each day. Those are not the same endeavors, they don't work in the same way (although sometimes they will overlap of course).
It is not enough to just recommend people to have a good lifestyle. That is a plus, but that will not get humanity to regular 100+ of healthy life years. We need actual new biological or genetic technology to do this.
I'm sorry to disappoint you, drugs (defined by the simple macromolecules we know them to be today) can supplement your body in doing only what it is already capable of.
Increasing lifespan more than that requires an entirely new paradigm or class of therapeutics. Like you said, we'll need entirely new biological/genetic technology to address the system-wide mutation and degradation of the body that inevitably occurs through the progression of time. That requires going into the realm of biotech/nanotechnology/etc. which as of now, we are still very far away from being able to produce. It will require many more years of basic research in a plethora of different fields before we can even begin to think about it in fact. Your best bet if you want to make it all the way to then is to follow the steps listed above.
> drugs (defined by the simple macromolecules we know them to be today) can supplement your body in doing only what it is already capable of.
Lots of drugs do things that your body is not capable of, and many drugs augment the way your body works in a way that is not possible without an external compound.
I tend to think of aging as an overall degradation of the system. For instance, there’s loss of hair cells in the ear that reduces hearing higher frequencies. There’s clouding of the eye lens as the proteins there aggregate. Long lived cells like neurons accumulate oxidation and probably die at some slow rate.
I can’t quite see how drugs which modulate existing biochemical pathways can stop, let alone reverse the processes I’ve named.
> I can’t quite see how drugs which modulate existing biochemical pathways can stop, let alone reverse the processes I’ve named.
I'm honestly mystified why this would be a mystery. Your cells have the blueprint to grow a whole new body, but clearly many of these pathways are dormant. Is it really so far fetched that a drug could reactivate some of these pathways?
Like, why is there a loss of hair in the ear when for the first few years of life, that hair grows instead of dies? There is even evidence that age reversal can and has been done:
The body forms structures over the course of development. But I don’t think it can replay those actions again. In places like the knee and eye lens, the cells that formed those structures did their job and dissolved their nuclei. I’m more familiar with the eye lens example so let’s go with that. The cells there are just bags of proteins and antioxidants. No nuclei, no mitochondria, no activity. Oxidation from the environment gradually damages those proteins and lead to cataracts. Everyone would eventually get cataracts if they could live forever.
DNA is not enough. There was coordination in time and space to construct the body during development, and the growing body has no damaged cells and structures to deal with.
> I tend to think of aging as an overall degradation of the system
Why do you do that? Why would you think it is correct?
To my knowledge that's a wrong interpretation.
Yes there is constant continuous damage to DNA and cells etc. But the body has mechanisms to repair that damage. It is the repairment that slows down during aging, and that is programmed by genetic and biological processes, like everything else in the body. Biologically, a cell can keep reproducing over and over again, it is no problem.
Put it simply, there is reversible damage and irreversible damage. Oxidized protein aggregates that the cell can’t degrade are an example of irreversible aggregates. Amyloid protein fibrils, although no longer implicated in disease, are another example of a stable, irreversible state. The process of repair slows down not due to programming but because the cells of the body get progressively worse at identifying and repairing damage, because the very machinery that carries out these processes, proteins, get damaged.
That’s a very good summarization of the problems we face in dealing with aging. No drug can fix the damage that is caused by it. We have very early therapies that try to jumpstart or uplift existing biological machinery like the various immunotherapies currently being targeted towards cancers, but that’s still just taking advantage of what is inherent to our bodies. Over time these processes inevitably begin to fail.
You have to engineer new machinery to replace/repair the failing processes for any chance at real longevity. The kind of things that will be capable of doing something like that will be extraordinarily complex, and to compare the drugs we have available today is akin to comparing an abacus to a modern supercomputer.
> Increasing lifespan more than that requires an entirely new paradigm or class of therapeutics. Like you said, we'll need entirely new biological/genetic technology to address the system-wide mutation and degradation of the body that inevitably occurs through the progression of time.
That's exactly what the drugs being discussed in this thread purportedly do. For instance, NMN allegedly repairs epigenetic factors that repair DNA damage, but which degrade as we age.
I guess you haven't heard of steroids. Taking 10x your natural level can increase your muscle strength above physiological limits. So there, you have the ability to reverse the degradation of muscle with aging.
Similarly, you can reverse other negative effects with other drugs. One thing at a time.
> can supplement your body in doing only what it is already capable of
Oh then I guess the body is perfectly capable of having lucid trips for hours like users report from a simple little molecule such as LSD. Good to know. /s
>Proper sleep, a complete diet, minimizing stress (I'm personally biased towards meditation), intermittent fasting, and vigorous cardiovascular exercise complemented by strength training
Yes, but the problem is this is such a broad brush stroke.
For example, most people who are chronically stressed will generally never be able to obtain relief. There is a common joke about abs being made in the kitchen not in the weight room, and another one about not being able to outrun a poor diet. The truth is the best diet in the world, cardio and strength training will never overcome the damaging effects of cortisol as a result of chronic stress.
The same for proper sleep. Its not just about 6-8 hours, its about quality. If you aren't getting quality sleep, most people don't have a solution. Then when they look for solutions its generally a bombardment of sleep products (from beds, to pillows, to supplements) that are backed by million/billion dollar companies that are targeting you when you perform a search for information/help.
As to intermittent fasting, that has become a major fad since the Nobel Prize for Autophagy (with the most popular implementation being a 8/16 time restricted eating "fast"). In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting).
Finally "a complete diet", not only is there no general consensus what that is, you generally can't even have a conversation about diet without triggering a flame war. It doesn't matter if you are WFPB, keto, vegan, vegetarian, paleo, carnivore...not only will people oppose your diet, they will aggressively attack it. I remember I once mentioned "detoxing" and couldn't believe people referring to it as voodoo, and telling me there is no such thing as detoxing the body, but then when I ask them what the function of the liver and kidneys are, and they had no idea.
Agreed as to your finale, most people have a pop culture understanding of physiology, but remain vehemently opposed to certain ideas largely accepted by alternative health communities. (And the functions, for those of you still unclear, are many including balancing the blood pH and removing actual toxins from the body.)
However, regarding fasting, one of the most recent studies (<1month, dec19) around is pretty compelling.(0) Though the breakdown is 6/18 vice 8/16 and it seems they do advocate for a weekly fast of 5/2 days (eat/fast). How's that for a weekend?
"In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting)."
I can't comment on how long it takes to achieve autophagy - I am happy to stipulate that you are correct.
However, digestion is a very all-encompassing, rigorous and expensive activity for your body. If we believe that there are more "cleanup" mechanisms than just autophagy, it's not much of a reach to suggest that we engage in extra digestion at the expense of these maintenance tasks.
>However, digestion is a very all-encompassing, rigorous and expensive activity for your body. If we believe that there are more "cleanup" mechanisms than just autophagy, it's not much of a reach to suggest that we engage in extra digestion at the expense of these maintenance tasks.
Make no mistake I think there are potential benefits to IF fasting such as these. For most people yes it will let their digestive system rest and even potentially reduce the overall intake of calories. Again it is all potential though, obviously not everyone needs to do IF to restrict calories if that is their goal, and there are ways to consume calories while simultaneously not digesting solid foods (that are typically outside the accepted scope of IF or fasting).
My point is the reason IF became a phenomena so widely discussed and implemented (edit: for increasing life span/expectancy) is directly related to the Nobel Prize in 2016; however, that work is related to autogaphy and fasting, not IF and IF related benefits. Edit:
>As to intermittent fasting, that has become a major fad since the Nobel Prize for Autophagy (with the most popular implementation being a 8/16 time restricted eating "fast"). In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting).
There's always OMAD (one meal a day). I generally fast 23 hours out of every 24. I rarely think about my next meal until I get home from work and it's time to cook something.
> most people who are chronically stressed will generally never be able to obtain relief
This really stood out to me. If this is how you feel, I strongly recommend trying out meditation. I at one point in my studies while in college felt the same, and it really is night versus day in being able to experience a life without constant stress/anxiety.
> The same for proper sleep. Its not just about 6-8 hours, its about quality. If you aren't getting quality sleep, most people don't have a solution.
Stress/anxiety from above is generally the most common cause of poor sleep. Fixing that will give quality sleep for the majority of people. The next thing to try is to check with your doctor whether you have sleep apnea as that's probably the second most common trigger. For some, sleep apnea is treatable with better sleeping posture and for others it will require more active work to resolve. A note that obesity is the most common cause of sleep apnea. The third most common cause is likely some kind of thyroid condition. More than that is probably going to be a case by case basis where you'll have to individually look at your genetic profile through something like SNPedia (https://www.snpedia.com/index.php/SNPedia) to try and pinpoint your underlying issue. Usually though, the first three things will cover the vast majority of people looking for better sleep.
> In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting
For most normal people, it's unrealistic to be able to do day fasts. That's why the 8/16 method is so popular. You'll still see benefits as you are incorrect that, there has to be a strict limit of precisely 20 hours to get beneficial effects. Autophagy like any other biological process in the body is a series of continuous interlinking upregulating and downregulating mechanisms that ensure homeostasis. Autophagy is always happening. It's just that the longer you fast, the more your body gets tilted towards consuming/recycling until of course you end up in starvation which is effectively just extreme autophagy.
> Finally "a complete diet", not only is there no general consensus what that is, you generally can't even have a conversation about diet without triggering a flame war.
A complete diet to the best of our knowledge, consists of getting enough macronutrients like protein, lipids, and carbohydrates in addition to an immense number of different micronutrients that while seemingly daunting in size are actually relatively easy to get enough of as long as you eat a diverse mixture of different foods. If that answer doesn't satisfy you, there have been many different studies and current ongoing ones as well to try and pinpoint all the essential trace nutrients the human body needs to survive. From the ones that we've been able to gather over the years, if you were to solely supplement yourself based on those listed, you'd probably be fine. Though it's likely that there would be some things missing.
>This really stood out to me. If this is how you feel, I strongly recommend trying out meditation. I at one point in my studies while in college felt the same
I run about 7-10 miles a day and mediate, and no I am not talking about me, I am talking about the effects of cortisol and chronic stress generally. And not to take away from the stress you felt in your studies, as I say stress is cortisol and the effects are the same no matter the trigger, but in the scheme of life stress in studies is very low. Consider people who have been through traumatic events war, rape, homelessness, kidnappings, murder of a loved one, the death of a child, etc... ]
>You'll still see benefits as you are incorrect that, there has to be a strict limit of precisely 20 hours to get beneficial effects.
I never said there are no beneficial effects of IF, caloric restriction is good for most people and IF helps that. However, I think you should read the actual Nobel Prize winner's papers and research before you say I am incorrect, or consider you are saying the Nobel Prize winner is incorrect, because I was quoting him.
>It's just that the longer you fast, the more your body gets tilted towards consuming/recycling until of course you end up in starvation.
No autophagy has a peak and it is far short of dying of starvation. Again read the work.
What makes sense to do personally is very different from what makes sense to research as a medical device or drug candidate. If a therapy has a 10% chance of extending lifespan by ten years, it's marginal for any particular person (given the current evidence), but a great candidate for a clinical trial.
Oh, I don't disagree. There's the entire burgeoning field of nootropics from which you can pick and choose as many supplements / drugs as you could want to test. An interesting point you might find, is that the nootropics which often have the greatest effect are the ones that help to deal with one or more of the items listed above.
For example, looking at some of the most common "life-extending / anti-aging" supplements people use which might hold promise of clinical efficacy:
[melatonin] -> proper sleep (usually there's an underlying issue of anxiety, stress, bad posture, sleep apnea, etc. that's being supplemented here)
[an innumerable count of different micronutrients] -> complete diet (those that see the most benefits are people that have deficiencies in those areas whether due to poor diet or genetic mutations from birth that lower efficiency of production but perhaps aren't so noticeable that they result in life threatening effects)
[metformin] -> intermittent fasting (which really ends up being the process of autophagy that you want to occur)
There's very little evidence that completely abstaining from meat (animal based protein) brings any meaningful advantages from the perspective of life span. In fact in general, it's far more difficult to build a complete diet eating vegan only. I of course do think there's a moral argument to a vegan lifestyle, and am a definitely a strong proponent on that end.
Personally, I think a vegetarian diet strikes a better balance that's also more sustainable in the long term, assuming that you also do care about maximizing life span as well.
Your link has some great information. Plants are highly nutritious, and people who don't get enough of them are probably unlikely to be as healthy as they could be.
That, however, doesn't preclude meat being beneficial as well. It's not an analog one is better than the other, and it doesn't mean you can't build a complete diet being vegan either. It's possible, in fact, to build a complete diet eating meat only as well if you really wanted to. Generally though, it's far more difficult, and you have to be pretty meticulous about what you eat in addition to probably having to supplement additional micronutrients into your diet to do so.
B12 you can get from a pill. The same stuff they inject into beef. [1]
So if you skip eating red meat, you can avoid the toxins from cooking, such as HCA and PAH [2], the exogenous cholesterol, atherosclerotic carnitine [3], hormones, etc. I think that's a better way to get B12.
If you feed cows corn all day every day, yes they need B12 injections. I buy beef from a local butcher and the beef comes from our local farm of pasture-raised cows. It's more expensive but because of this it limits my beef intake to a few times a month.
liver == steak * 1000
Only problem is being able to stomach liver a few days every month. I know it's a super food but I'll be damned if I can eat it more than once every few months.
You shouldn't look at doing anything else until you've at minimum mastered all of the listed items above. Nothing else will have as much outsized impact.