The local Belgian/European life-extension non-profit Heales is giving away prizes for whoever can make an interesting short movie about life extension. The first prize is €3000 (around $3386 as of today), other prizes being various gifts. You more or less just need to send a link pointing to the uploaded media along with your contact info to info@heales.org once you're done.

While we're at it you don't need to be European, let alone Belgian to participate, and it doesn't even need to be a short movie anyway. For instance a comic strip would fall within the scope of the rules as specified here : (link to a pdf file)(or see this page on fightaging.org). Also, sure, the deadline is by now supposed to be a fairly short-term September the 21st, 2015, but it is extremely likely this will be extended (this might be a pun).

I'll conclude by suggesting you read the official pdf with rules and explanations if you feel like you care about money or life-extension (who doesn't ?), and remind everyone of what happened last time almost everyone thought they shouldn't grab free contest money that was announced on Lesswrong (hint : few enough people participated that all earned something). The very reason why this one's due date will likely be extended is because (very very) few people have participated so far, after all.

(Ah yes, the only caveat I can think of is that if the product of quality by quantity of submissions is definitely too low (i.e. it's just you on the one hand and on the other hand that one guy who spent 3 minutes drawing some stick figures, and your submission is coming a close second), then the contest may be called off after one or two deadline extensions (also in the aforementioned rules).).

It should be emphasized that back-of-the-envelope calculations, such as the one given in this post, ought to be adjusted to account for the fact that interventions can look much more cost-effective than they are, especially when the interventions were only shallowly investigated.

Previously, Givewell has looked into the cost-effectiveness of life sciences funding, as well as publishing a simple estimate of the impact of the average dollar spent on cancer research, which suggested that, in the past, each $2790 spent on cancer-relevant biomedical research in the US added one year of life lived (YLL) to the life of a US resident. Givewell has also interviewed Aubrey de Grey of the SENS foundation. Owencb has previously estimated the cost-effectiveness of funding SENS/ anti-aging research as being around $50 per QALY. Aubrey de Grey has previously been averse to giving explicit cost-effectiveness estimates regarding how many QALYs would be gained per unit of funding supplied to SENS, though he has been clear that SENS's funding needs are "$100 million per year for each of the next ten years".

This part of the post will consist of me using lots of best guesses to produce something vaguely resembling a cost-effectiveness estimate for SENS. You should not take this cost-effectiveness estimate literally.

If SENS needs one billion dollars to ensure that rejuvenation technologies that give individuals 30 extra years of healthy life are available to the public in 30 years, we might (completely arbitrarily) assume that someone else will come along and fund SENS in ten years if we don't contribute to funding SENS today. This means that if we fund SENS today instead waiting for it to be hypothetically funded in ten years from now, about ten times the number of people who die each year would live 30 years of healthy life that they wouldn't have lived otherwise. Given that there are about 57 million deaths per year worldwide, this translates to about 17 billion YLLs lost by waiting ten years to fund SENS; since SENS ostensibly requires only 1 billion of philanthropic funding, this implies that $0.059 of funding for SENS produces a YLL.

Of course, regenerative medicine won't be free to the people receiving it, and I have no idea how to account for this, given that I don't have a good idea of how much regenerative therapies will initially cost. The above estimate hasn't been adjusted to account for the fact that there is a time-delay between when funding is provided, and when the benefits of regenerative therapies are available to the public. Perhaps Aubrey isn't well-calibrated, and the "$100 million per year for ten years" figure is entirely wrong. It may be the case that starting work on SENS's research agenda earlier rather than later would allow certain people who would have otherwise died to live until aging escape velocity is reached, which would have lots of utility. There are plenty of other issues with this cost-effectiveness estimate which I am sure that readers could point out.

The point I wanted to make, though, was that maybe, possibly, SENS is competitive with GiveWell's top charities-- I'm legitimately not sure whether I would fund SENS or GiveWell if I were making a charitable donation today. Does anyone have any further thoughts on this topic?

Imagine you had the following at your disposal:

• A Ph.D. in a biological science, with a fair amount of reading and wet-lab work under your belt on the topic of aging and longevity (but in hindsight, nothing that turned out to leverage any real mechanistic insights into aging).
• A M.S. in statistics. Sadly, the non-Bayesian kind for the most part, but along the way acquired the meta-skills necessary to read and understand most quantitative papers with life-science applications.
• Love of programming and data, the ability to learn most new computer languages in a couple of weeks, and at least 8 years spent hacking R code.
• Research access to large amounts of anonymized patient data.
• Optimistically, two decades remaining in which to make it all count.

Imagine that your goal were to slow or prevent biological aging...

1. What would be the specific questions you would try to tackle first?
2. What additional skills would you add to your toolkit?
3. How would you allocate your limited time between the research questions in #1 and the acquisition of new skills in #2?

Thanks for your input.

Update

I thank everyone for their input and apologize for how long it has taken me to post an update.

I met with Aubrey de Grey and he recommended using the anonymized patient data to look for novel uses for already-prescribed drugs. He also suggested I do a comparison of existing longitudinal studies (e.g. Framingham) and the equivalent data elements from our data warehouse. I asked him that if he runs into any researchers with promising theories or methods but for a massive human dataset to test them on, to send them my way.

My original question was a bit to broad in retrospect: I should have focused more on how to best leverage the capabilities my project already has in place rather than a more general "what should I do with myself" kind of appeal. On the other hand, at the time I might have been less confident about the project's success than I am now. Though the conversation immediately went off into prospective experiments rather than analyzing existing data, there were some great ideas there that may yet become practical to implement.

At any rate, a lot of this has been overcome by events. In the last six months I realized that before we even get to the bifurcation point between longevity and other research areas, there are a crapload of technical, logistical, and organizational problems to solve. I no longer have any doubt that these real problems are worth solving, my team is well positioned to solve many of them, and the solutions will significantly accelerate research in many areas including longevity. We have institutional support, we have a credible revenue stream, and no shortage of promising directions to pursue. The limiting factor now is people-hours. So, we are recruiting.

Thanks again to everyone for their feedback.

The following is authored by Colby Davis. I am posting for him because he doesn't have an account with any karma. Someone recently requested numbers on cryo preservation costs. I'll note that my own opinion is that for young people unlikely to die investing money in research is a better bet than investing directly in your own preservation.

Here is the link for the spreadsheet. Either download it or create a copy for yourself to edit.

Hey rationalists, here's the spreadsheet I presented the other night. For those who weren't there but are interested, this is a tool I designed to break down the costs associated with signing up for cryonics under different methods of financing it. Here are some instructions for using it.

Column B is where the user puts all the inputs: age, sex, probability you think that if you are frozen you will someday be successfully revived, and discount rate (for those unfamiliar with the term, this is like the reverse of an interest rate, the rate at which cash flows become less valuable to you as they extend further out into the future).

Column D is the probability that you will die in the next 20 years (the typical term for a term life insurance policy). It is calculated based on the "life table" sheet, which i stole from a government actuarial table online.

Column E is your current life expectancy, the number of additional years you have a roughly 50% chance of surviving through.

Column F is how much the monthly fee for a 20 year, $100,000 life insurance policy would cost you, assuming "exceptional" health, as determined by the top result at http://www.term4sale.com/

Column G is the present value of that policy, using your discount rate. This means that you should be indifferent between paying this amount right now and paying the figure in column F every month for the next 20 years.

Column H is the probability that you will die within the next 20 years AND sometime thereafter be successfully revived from cryogenic suspension, making the heroic assumption that your probability belief in column B is true.

Column I is simply the dollar present value amount spent per 1 percentage point reduction in (permanent) death. This is the value you want to consider most when deciding whether to sign up or not.

The next columns consider the alternative means of paying for a cryonics policy, saving up and investing in the stock market until you have enough money to pay for it outright.

Column K gives the future value after 20 years of investing the amount you would have spent on an insurance policy in the stock market instead, as well as the present value of that figure to you now, discounted back at the rate you gave. (This is not necessarily pertinent to the cryonics decision but is provided for comparison)

Column L is the amount you would have to invest monthly to have an expected future value of $100,000 by the end of your life expectancy.

Column M is the present value of foregoing that monthly amount for the rest of your life expectancy.

Column N is the probability you will die after you life expectancy (50%) AND be successfully revived assuming yours p-value.

And finally column O is the same measure as in Column I, using this alternative plan. A lower value in one column or the other (most of you will find column O to be the lesser value) means that you can reduce your probability of permanent death cheaper (or, reduce your probability of death by a greater amount for the same dollar amount) by pursuing the cheaper strategy.

Hope you enjoy!

- Colby  

P.S.

There was a discussion at the meeting about whether the figure in column N was too high because it failed to account for the probability that poor stock market performance may leave you without enough money to afford the cost of cryonics. I believe this is false because since long-run stock returns distributions and life expectancies are approximately normally distributed and independent of one another, the chance that you will die late with a poor return (thus unable to freeze your head) is almost perfectly offset by the chance that you will die early with a great return (thus still able to freeze your head). So it's not that the mean is too high, but merely that there is a variance around it. I was trying to figure out how to work this into the spreadsheet but figured the uncertainty of our beliefs about cryonics was much more a confounding factor here than the probability distribution of possible stock-returns-time-paths.

Followup to: Lifestyle interventions to increase longevity.

What does it mean for exercise to be optimal?

• Optimal for looks
• Optimal for time
• Optimal for effort
• Optimal for performance
• Optimal for longevity

There may be even more criteria.

We're all likely going for a mix of outcomes, and optimal exercise is going to change depending on your weighting of different factors. So I'm going to discuss something close to a minimum viable routine based on meta-analyses of exercise studies.

Not knowing which sort of exercise yields the best results gives our brains an excuse to stop thinking about it. The intent of this post is to go over the dose responses to various types of exercise. We’re going to break through vague notions like “exercise is good” and “I should probably exercise more” with a concrete plan where you understand the relevant parameters that will cause dramatic improvements.

TLDR: Study on death avoidance, which interests a lot of people here, and commentary on what sort of informative priors we should have about health hypotheses.

From Steve Sailer, who is responding to Andrew Gelman, who got sent this study. An observational study showed that people who consumed nuts were less likely to die; Gelman points out that the study's statistics aren't obviously wrong. Sailer brings up an actual RCT of Lipitor from the 90s:

The most striking Lipitor study was one from Scandinavia that showed that among middle-aged men over a 5-year-period, the test group who took Lipitor had a 30% lower overall death rate than the control group. Unlike the nuts study, this was an actual experiment.

That seemed awfully convincing, but now it just seems too good to be true. A lot of those middle-aged deaths that didn't happen to the Lipitor takers didn't have much of anything to do with long-term blood chemistry, but were things like not driving your Saab into a fjord. How does Lipitor make you a safer driver? 

I sort of presumed at the time that if they had taken out the noisy random deaths, that would have made the Lipitor Effect even more noticeable. But, of course, that's naive. The good folks at Pfizer would have made sure that calculation was tried, so I'm guessing that it came out in the opposite direction of the one I had assumed. Guys who took Lipitor everyday for five years were also good about not driving into fjords and not playing golf during lighting storms and not getting shot by the rare jealous Nordic husband or whatever. Perhaps it was easier to stay in the control group than in the test group?

Here’s how I would approach claims of massive reductions in overall deaths from consuming some food or medicine:

Rank order the causes of death by how plausible it is that they are that they are linked to the food or medicine. For example:

1. Diabetes

2. Heart attacks

3. Strokes

4. Cancer

5. Genetic diseases

6. Car accidents

7. Drug overdoses

8. Homicides

9. Lightning strikes

If this nuts-save-your-life finding is valid, then the greater effects should be found in causes of death near the top of the list (e.g., diabetes). But if it turns out that eating nuts only slightly reduces your chances of death from diabetes but makes you vastly less likely to be struck by lighting, then we’ve probably gotten a selection effect in which nut eaters are more careful people in general and thus don’t play golf during thunderstorms, or whatever.

Table 3 of the paper breaks out the hazard ratios by cause of death. The most impressive effects (as measured by the right tail of the 95% CI for pooled men and women for any nut)¹ are Heart Disease, All Causes, Other Causes, Cancer, Respiratory Disease, Stroke, Infection, Diabetes, Neurodegenerative Disease, and Kidney Disease.

Steve's categories and the paper's categories don't overlap very well. But it looks to me like if you follow Steve's logic, it's reasonable to believe that nuts have a protective effect against heart disease, and then most of the other effects or non-effects have a common cause with nut consumption, like healthiness / conscientiousness / whatever, rather than being caused by nut consumption. Note the strong negative relationships between nut consumption and BMI or smoking, and the strong positive relationships between nut consumption and physical activity or intake of fruits, vegetables, or alcohol. The hazard ratios are calculated controlling for those variables, but it's still reasonable to see there being a hidden 'health-consciousness' node which noisily affects all of those nodes.

It's also interesting to look at the negative results- the hazard ratio for neurodegenerative disease and stroke was roughly 1, implying that nut-eaters and non-nut eaters had comparable risks, despite 'other causes' having a hazard ratio of 0.87. That weakly implies to me that either health consciousness has no impact on neurodegenerative disease and stroke, or that nuts are harmful for those two categories.

Since heart disease is a huge killer (24% of all deaths in the study group), this study seems like moderate evidence in favor of eating nuts, but it's likely that the total study's effect is overstated. (The study also suggests that tree nuts are probably superior to peanuts; I know various QS people have raised concerns that the kind of nut matters significantly.)

1. This is a heuristic for impressiveness, not the point estimate. It looks like nuts have the strongest effect for kidney disease, with a mean hazard ratio estimate of 0.69- but the upper bound of the 95% CI is 1.26, because only a handful of people died due to kidney disease. The heart disease hazard ratio estimate is 0.74 (0.68-0.81), which is much more believable, even though the point estimate is slightly higher. The point estimate for diabetes is 0.80 (0.54-1.18), which has a mean estimate that's only slightly worse, but diabetes again killed far fewer than heart disease. If you order them by point estimates, the paper is stronger evidence for nuts being useful for dietary reasons, and which method you prefer depends on your priors for how representative this sample is.

There are two confusing but potentially important papers in the Jan. 25 2013 Science on long-term memory (LTM) formation in fruit flies:

Pierre-Yves Placais & Thomas Preat. To favor survival under food shortage, the brain disables costly memory. 339:440-441.

Yukinori Hirano et al. Fasting launches CRTC to facilitate long-term memory formation in Drosophila. 339:443-446.

These papers categorize long-term memory formation along three axes.

• Aversive vs. appetitive:  Actions that the brain interprets as helping it avoid something, vs. actions that help it attain something.
• Fasting-dependent (fLTM) vs. spaced training-dependent (spLTM):  fLTM is formed in a single learning episode, but only at the time that an organism first obtains food after a long fast. spLTM does not require fasting but requires repeated training.
• LTM vs. ARM: Memories that require protein synthesis (LTM) vs. "anesthesia-resistent memory" (ARM), which does not.  (The papers don't explain what ARM might correspond to in humans.)

The relationship between these is unclear, particularly as each of these three axes is claimed at various times to determine whether memory can be learned in a single training cycle (appetitive, fLTM, and/or ARM) or not (aversive, spLTM, and/or LTM).  But these things appear to be likely, or at least to be reasonable hypotheses, if these pathways are conserved in humans:

• How quickly you learn something depends on how much you've eaten recently.  You learn most quickly immediately after ending a long fast. Your brain thinks you just learned something that saved it from starvation. (But note that a 1-day fast for a fruit fly could be compared to a human fasting for months.)
• How quickly you learn something depends on whether your brain thinks that this knowledge is to avoid something bad (slow learning) or to attain something good (fast learning).
• Almost all of the mutations that extend lifespan in organisms from yeast to humans impact the FOXO3a vs. mTORc1 axis (to use the human analogs).  Expressing FOXO3a inhibits mTORc1 and extends lifespan in various ways; producing and assembling more mTORc1 inhibits FOXO3a and promotes protein synthesis, growth, reproduction, tissue repair, and immune response.  We already know that extending lifespan, in general, is antithetical to building muscle.  It may also be antithetical to forming long-term memories.  This makes sense.
• Learning rate can be increased by expressing or inhibiting  proteins involved in these responses.  Hirano et al. focus on activating a cAMP-regulated transcriptional coactivator (CRTC) by dephosphorylating it in order to invoke fLTM.  They were able to do this and enable flies to learn quickly without fasting followed by feeding.

I'd really appreciate it if somebody would do a literature review and a comparison of the pathways involved to those in humans, and summarize their findings.

Why Don't Futurists Try Harder to Stay Alive?, asks Rob Wiblin at Overcoming Bias

Suppose you want to live for more than 10 thousand years. (I'll assume that suffices for the "immortalist" designation). Many here do.

Suppose in addition that this is by far, very far, your most important goal. You'd sacrifice a lot for it. Not all, but a lot.

How would you go about your daily life? In which direction would you change it?

I want to examine this in a sequence, but I don't want to write it on my own, I'd like to do it with at least one person. I'll lay out the structure for the sequence here, and anyone who wants to help, by writing an entire post (these or others), or parts of many, please contact me in the comments, or message. Obviously we don't need all these posts, they are just suggestions. The sequence won't be about whether it is a good idea to do that. Just assume that the person wants to achieve some form of Longevity Escape Velocity. Take as a given that it is what an agent wants, what should she do?

1) The Ideal Simple Egoistic Immortalist - I'll write this one, the rest is up for grabs.

Describes the general goal of living long, explains it is not about living long in hell, about finding mathy or Nozickian paradoxes, about solving the moral uncertainty problem. It is just simply trying to somehow achieve a very long life worth living. Describes the two main classes of optimization 1)Optimizing your access to the resources that will grant immortality 2)Optimizing the world so that immortality happens faster.  Sets "3)Diminish X-risk" aside for the moment, and moves on with a comparison of the two major classes. 

2) Everything else is for nothing if A is not the case -

Shows the weaker points (A's) of different strategies. What if uploads don't inherit the properties in virtue of which we'd like to be preserved? What if cryonics facilities are destroyed by enraged people? What if some X-risk obtains, you die with everyone else? What if there is no personal identity in the relevant sense and immortality is a desire without a referent (a possible future world in which the desired thing obtains)? and as many other things as the poster might like to add.

3) Immortalist Case study - Ray Kurzweil -

Examines Kurzweil strategy, given his background (age, IQ, opportunities given while young etc...). Emphasis, for Kurzweil and others, on how optimal are their balances for classes one and two of optimization.

4) Immortalist Case study - Aubrey de Grey -

5) Immortalist Case study - Danila Medvdev -

Danila has been filming everything he does hours a day. I don't know much else, but suppose he is worth examining.

6) Immortalist Case study - Peter Thiel

7) Immortalist Case study - Laura Deming

She's been fighting death since she was 12, went to MIT to research on it, and recently got a Thiel fellowship and pivoted to fundraising. She's 20.

8) Immortalist Case study - Ben Best

Ben Best directs Cryonics Institute. He wrote extensively on mechanisms of ageing, economics and resource acquisition, and cryonics. Lots can be learned from his example.

9) Immortalist Case study - Bill Faloon

Bill is a long time cryonicist, he founded the Life Extension Foundation decades ago, and to this day makes a lot of money out of that. He's a leading figure in both the Timeship project (super-protected facility for frozen people) and in gathering the cryonics youth togheter.

10) How old are you? How much are you worth? How that influences immortalist strategies. - This one I'd like to participate.

11) Creating incentives for your immortalism - this one I'll write

How to increase the amount of times that reality strikes you with incentives that make you more likely to pursue the strategies you should pursue, being a simple egoistic immortalist.

12, 13, 14 .... If it suits the general topic, it could be there. Also previous posts about related things could be encompassed.

Edit: The suggestion is not that you have to really want to be the ideal immortalist to take part in writing a post. My goals are far from being nothing but an immortalist. But I would love to know, were it the case, what should I be doing? First we get the abstraction. Then we factor in everything else about us and we have learned something from the abstraction.

Seems people were afraid that by taking part in the sequence they'd be signalling that their only goal is to live forever. This misses both the concept of assumption, and the idea of an informative idealized abstraction.

What I'm suggesting we do here with immortality could just as well be done with some other goal like "The Simple Ideal Anti-Malaria Fighter" or "The Simple Ideal Wannabe Cirque de Soleil".      

So who wants to play?

Edit: Dangerously misleading on one crucial point.

This started out as a short reply to the Less Wrong post Minimum Viable Workout Routine. Unfortunately I was unable to summarise my points sufficiently, so this reply grew into a post of it's own. I realize that the following is a bit rude to the original poster, and I apologize. Minimum Viable Workout Routine seems to be backed solely by anecdotal personal experience. The majority of the post, which addresses strength training seems decent, and not obviously wrong. However, the following paragraph is dangerously wrong:

A note about cardio: Cardiovascular capacity (V02 max) has shown a high degree of correlation to all cause mortality.  Why aren't I recommending cardio?  Because the only way to increase V02 max is with high intensity exercise.  Between high intensity weight lifting and high intensity cardio, high intensity weightlifting easily wins for a newbie.  A newbie, especially a significantly out of shape one, will not be capable of a level of cardio exertion that results in a significant adaptation.  This can result in a lot of effort with very little in the way of improvement.  This is soul-destroyingly frustrating.

Leaving this uncontested could be dangerous to your health. As we shall see, cardiovascular capacity is indeed important to survival and longevity. It is also quite easily trainable, it needs not be soul crushingly frustrating, and it should not be overlooked. 

A couple of cool findings from the physiology of exercise:

Instead of having me trying to convince you, we'll take a look at the science, and see what we find.

You can assume with reasonable confidence that the findings are valid, well-corroborated, and furthermore, the findings quoted in this post have been found to apply to the general population, to the untrained, the athlete, the elderly, and the ill, even though I'm only able to present here a selection of these results.

Human physiology, and its response to exercise is surprisingly stable across genders, race, age and physical fitness. What works for the well trained athlete will also work for the utter newbie, the obese, and patients with heart disease.

Strength training is also important to health, increases in maximal strength of the large muscle groups tends to cause large increases in endurance, as measured in time to exhaustion. Why? Because if your muscles have to work slightly less hard at each movement, relative to the one repetition maximum of the muscle, you can work at moderate to high intensities for much longer.

So, let's first see that a brief strength training intervention can dramatically increase endurance:

Maximal Strength Training Improves Running Economy in Distance Runners

Purpose: The present study investigated the effect of maximal strength training on running economy (RE) at 70% of maximal oxygen consumption (VO2max) and time to exhaustion at maximal aerobic speed (MAS). Responses in one repetition maximum (1RM) and rate of force development (RFD) in half-squats, maximal oxygen consumption, RE, and time to exhaustion at MAS were examined.

Methods: Seventeen well-trained (nine male and eight female) runners were randomly assigned into either an intervention or a control group. The intervention group (four males and four females) performed half-squats, four sets of four repetitions maximum, three times per week for 8 wk, as a supplement to their normal endurance training. The control group continued their normal endurance training during the same period.

Results: The intervention manifested significant improvements in 1RM (33.2%), RFD (26.0%), RE (5.0%), and time to exhaustion at MAS (21.3%). No changes were found in VO2max or body weight. The control group exhibited no changes from pre to post values in any of the parameters.

Conclusion: Maximal strength training for 8 wk improved RE and increased time to exhaustion at MAS among well trained, long-distance runners, without change in maximal oxygen uptake or body weight

So a maximal strength training exercise of maybe 10 minutes, 3 times per week, for eight weeks, resulted in an increase in time to exhaustion of ~20% in well trained runners. So increases in strength can lead to large gains in endurance.

Cool, because endurance training is important. Endurance training makes you die less often, on average:

Exercise Capactity And Mortality Among Men Referred For Exercise Testing

Background: 

Exercise capacity is known to be an 

important prognostic factor in patients with cardiovascular disease, but it is uncertain whether it predicts 

mortality equally well among healthy persons. There 

is also uncertainty regarding the predictive power of 

exercise capacity relative to other clinical and exercise test variables. 

Methods: We studied a total of 6213 consecutive 

men referred for treadmill exercise testing for clinical 

reasons during a mean (±SD) of 6.2±3.7 years of follow-up. Subjects were classified into two groups: 3679 

had an abnormal exercise-test result or a history of 

cardiovascular disease, or both, and 2534 had a normal exercise-test result and no history of cardiovascular disease. Overall mortality was the end point. 

Results: There were a total of 1256 deaths during the 

follow-up period, resulting in an average annual mortality of 2.6 percent. Men who died were older than 

those who survived and had a lower maximal heart 

rate, lower maximal systolic and diastolic blood pressure, and lower exercise capacity. After adjustment for 

age, the peak exercise capacity measured in metabolic 

equivalents (MET) was the strongest predictor of the 

risk of death among both normal subjects and those 

with cardiovascular disease. Absolute peak exercise capacity was a stronger predictor of the risk of death than 

the percentage of the age-predicted value achieved, 

and there was no interaction between the use or nonuse of beta-blockade and the predictive power of exercise capacity. Each 1-MET increase in exercise capacity 

conferred a 12 percent improvement in survival. 

Conclusions: Exercise capacity is a more powerful 

predictor of mortality among men than other established risk factors for cardiovascular disease. (N Engl 

J Med 2002;346:793-801.)

If you want to live long and prosper, you should train your body, most importantly your heart, to be able to work hard when you can. So that it can work hard for you when it must fight for your life. With that, let us have a look at endurance training in the elderly:

Effects of High-Intensity Endurance Training on Maximal Oxygen Consumption in Healthy Elderly People

Each 60-minute training session included four repetitions of exercise at approximately 85% to 95% of maximal heart rate separated by 4-minute rest periods. The control group was encouraged to perform no additive strength or endurance training during the study period. Maximal oxygen consumption increased significantly (p < .05) (13.2%) in the TG compared to the CG. Walking economy and maximal walking speed were unchanged after the training intervention. This training study demonstrates that high-intensity endurance training significantly improves VO2 max in older adults.

Why is this interesting? Well, it seems that old people respond the same to vigorous exercise, as do young people. 

But! They tend to do less of it, and consequently they gradually suffer worse health. I'm oversimplifying, but there is a causal path from physical inactivity with old age, (not because of old age) which leads to deterioration of health which leads to death. If you are reaching retirement age, or you know people who are, try to get them to move their butts before it's too late. And don't stop moving. Don't stop moving even if you suffer heart failure. Let's have a look at the effects of vigorous training in patients with heart disease:

Interval and Strength Training in CAD Patients:

This study sought to study the effect of high intensity aerobic interval endurance training on peak stroke volume and maximal strength training on mechanical efficiency in coronary artery disease (CAD) patients. 8 CAD patients (age 61.4 ± 3.7 years) trained 30 interval training sessions with 4 × 4 min intervals at 85-95% of peak heart rate while 10 CAD patients (age 66.5 ± 5.5 years) trained 24 sessions of maximal horizontal leg press.

In the interval training group peak stroke volume increased significantly by 23% from 94.1 ± 23.0 mL · beat (-1) to 115.8 ± 22.4 mL · beat (-1) (p<0.05). Peak oxygen uptake increased significantly by 17% from 27.2 ± 4.5 mL · kg (-1) · min (-1) to 31.8 ± 5.0 mL · kg (-1) min (-1) (p<0.05) in the same group. In contrast, there was no such exercise training-induced change in peak stroke volume or peak oxygen uptake in the maximal strength training group, despite a 35% improvement in sub maximal walking performance.

So this is what heart patients get in return for sixteen minutes, three times a week for two and a half months. If you're still breathing, and able to move by your own power, you are capable of the level of cardio exertion that leads to significant adaptation. You don't necessarily have to run fast, you just need to be able to get your heart rate to 85-95% of your maximum heart rate, repeatedly. For a CAD patient or an overweight person, this could mean a brisk walk. If you're out of shape,  you don't have to fly across the terrain at amazing speed for your heart to get all excited.

How, exactly, does endurance training keep people healthy and alive?

Repeated intervals of brief, but high intensity endurace training causes increased stroke volume of the heart, when working at peak capacity. This carries over into the resting state, and lowers your resting pulse, your blood pressure, increases your maximal oxygen uptake, increases your working capacity when healthy, makes you less likely to get ill. If you get ill, your heart will be better at keeping you alive.

Closing thoughts:

Should you trust my opinion? I've only taken a single university course in exercise physiology. You should not trust my opinion, and this is not professional advice. But my opinion is backed up with well-corroborated scientific findings, and you should probably trust those.

The course i took was excellent. The teaching professors were were former national team coaches, they have applied their research to great effect on healthy, untrained students, CAD patients, COPD patients, youth athletes, elite athletes and billion dollar soccer teams.

Pursuing a regime of maximal strength training and high intensity interval training, you should see evident and mutually reinforcing gains in strength and endurance, and you'll not stop seeing benefits, even at the level of 100 million dollar soccer players. (Endurance and Strength Training for Soccer Players)

An final anecdote of my own:

I used to find physical exercise dis-congruent with my geek identity, I found it boring, painful, useless. Learning the very basics of exercise physiology, along with some nerdy details makes working out seem important. It helps to know why I'm doing it, I know what the expected effects are, and the expected sizes of the effects, how to avoid training fatigue, track my heart rate, track my progress, and on the whole, see that I'm on track to results like those mentioned in the studies above. I find it fun to try and figure out what is happening, and approach working out as something of a puzzle to be solved. Exercise, or the lack of it, is an experiment in health.

Although there are no long-term scientific studies of calorie restriction in humans, there are religious groups, cults, and ascetics who voluntarily practice calorie restriction or intermittent fasting. Presumably there have been tens or hundreds of thousands of people who have practiced calorie restriction throughout most of their adult lives. There were/are probably also groups that involuntarily practice calorie restriction - servants, slaves, prisoners, or people who simply regularly don't have enough to eat.

If calorie restriction has a dramatic effect on life expectancy in humans, shouldn't we expect to observe extended life expectancy in at least some groups? Or would each of these groups likely have some mitigating circumstances that would shorten their lifespans, such as lack of medicine?

With an hour on Google, I found some references to Okinawa, to monks on Mount Athos, and to similar groups. In no case was there a reasonable claim of life expectancy over 90 (which would represent just a 10% improvement over life expectancy in Japan).

This paper reviews the evidence on calorie restriction in humans and other animals, including discussion of religious fasting, but there's no evidence there of fasting extending lifespan.

I found a few other sources where people asked this question (or made this point as an attack on CR), but I haven't yet found any good answers on the subject, and didn't find any discussion on LessWrong yet.

Heinlein imagined the Howard Foundation as a group founded by a millionaire dying of "old age" in mid-life; founded to encourage long lived people to have children together using financial incentives with the goal of breeding extra long-lived humans.

Our world has many billionaires, typically older rather than younger people ( Forbes list - few under 50 ); middle aged Bill Gates has donated his fortune to normal kinds of charity, elder Warren Buffett has as well, youthful Mark Zuckerberg has pledged his too, all healthy. Steve Jobs is worth over a billion dollars and has been criticised for his lack of public philanthropy, he's also CEO of a company with $60 billion in reserve, and suffering serious health problems.

In short, we live in a world where there are rich people, and where you hear the idea of "rich old white men spending a lot on medical treatments to benefit rich old white men" but at the same time, Aubrey De Gray style serious discussion of longevity is rare  and much medical spending goes on alleviating and curing the problems of old age rather than avoiding them.

Sergey Brin has donated $50 million towards Parkinson's research based on DNA tests showing he has a 50% chance of getting it, yet at the moment he has a much higher probability of getting old-age and a net worth of $10-15 billion.

Is our world one where something analagous to the Howard Foundation will appear? Let's pull some numbers from thin air and say that means someone dying and leaving pretty much all of their estate of more than $200 million to fund longevity research/treatment in some way. If so, it might be something done in private that we would not hear of, so what would be indicators that it might be about to happen, or might have happened already? And if an ill middle aged technology billionaire with change-the-world drive doesn't do it, then who?

(I consider significant increases in lifespan (100 healthy years, 150 total years, or more) nearly inevitable at some nonspecific time in the future, given a world where humans continue to develop technology improvements, remain primarily biological, and avert or avoid existential risks and government restrictions on it. I also consider that dying and leaving money to The Gates Foundation is a good cause arguably much better than longevity research, wheras dying and leaving hundreds of millions to heirs / dogs homes / art / etc. is not).