Global Consequences of Increased Human Longevity

I am a passionate life extensionist.  I am a passionate conservationist.  I have been living with a contradiction, increasingly stark as my understanding of both these causes, and my commitment to them deepens.

Nearly 20 years ago, I first became convinced by a variety of experimental evidence that aging is programmed into our genes by evolution.  It was five years after that that I had my first inkling how this could be.  This led to a study of evolved population regulation, and I became exquisitely aware of the entanglement of evolution and ecology.

Why would evolution create something as antithetical to the interests of her children (individually) as aging unto death?  A gene for aging is the opposite of a selfish gene.  And yet it is abundantly clear that we have genes* with no other purpose than to kill us.  Suicide genes.

My principal contribution to the field of aging research is the Demographic Theory of Aging, which says that aging evolved for the purpose of population stabilization.  There have been other theories of programmed aging in the past, usually based on the need for population turnover to assure adaptability, ongoing evolution and the ability of a population to change as conditions change.  What I demonstrated (first in a 2006 paper ) is that population dynamics provides a far more potent selective force than this.  Yes, the need to maintain population diversity and to change over time is certainly real .  But (for animals) the need to avoid population overshoot and subsequent crashes to extinction is far more urgent (not so for plants).  All animals depend on an ecosystem, and if they grow faster than their ecosystem, they are doomed.  Not doomed “eventually” in some abstract, far-off morality tale.  They are doomed within a generation or two.

Every animal population must have the latent capacity to grow quite rapidly in a pinch.  You can translate this to mean, roughly, that a population must be able to double in each generation when it is threatened or expanding freely into a new and fertile environment.  Human families in indigenous cultures can produce 6 or 7 babies, 4 of which survive to breed.  Roundworms can lay 300 eggs, 2 of which survive to breed**.  And, of course, microbes reproduce by cloning and double exactly with each generation.

art by Maddy Ballard

art by Maddy Ballard

But the doubling of a population that is already at carrying capacity can spell disaster.  Every blade of grass is eaten, or every rabbit is hunted, or every tree is denuded, and the ecosystem crumbles from the bottom up.

An ecosystem is a food web–predator and prey, the predator’s predator and the prey’s prey, multiply, connected and entangled, in an intricate network of interdependencies.   Stability of the network does not come for free.  There is no “invisible hand” that produces a grand harmony from a thousand selfish actors.  Rather, there is deep and ongoing coevolution.  Natural selection has taught each species cooperation and restraint via a billion years of tough love.  Those species that overreached to trash their own ecosystems brought their ecosystems crashing down, and their rapacious behaviors died with them.

(To this thesis, scientists in diverse fields say, “of course–that’s the essence of natural selection”.  But professional evolutionists have been trained to deny that such processes as this can occur.  Many still insist that evolution can only work to promote selfishness, never cooperation.)

Food web

Ecosystems are resilient.  There is an ability to bounce back after disturbance, from a natural disaster or the loss of a keystone predator.  This, too, is a property honed by natural selection, a strength of the community that has evolved gene-by-gene in its component species.  The unexpected happens, and the ecosystem has to deal with it.  Those ecosystems that can’t recover from an invasion or a decade of bad weather have long ago disappeared from the biosphere.

But recovery of an ecosystem requires time.  Bouncing back after a small disruption may require a dozen years or a dozen dozen.  Bouncing back from a major geologic or climate event requires thousands of years.  And in the history of multicellular life there have been five major extinctions.   Each time, the biosphere required tens of millions of years to recover.

We are now in the midst of the sixth global extinction , and as far as archaeology can tell, the anthropocene extinction is as deep and as rapid as any the earth has seen.

And how did we get here?  I believe the road to the Sixth Extinction was paved with ideology.  I speak not just of the Biblical ideology that says it is our place to “be fruitful and multiply, and fill the earth and subdue it; and have dominion over the fish of the sea and over the birds of the air and over every living thing that moves upon the earth.” [Genesis 1:28]  There is also the dominant version of Darwinian ideology that admits no explicit need for cooperation, but celebrates the creative power of selfishness.  Worst, perhaps, is the capitalist ideology that assigns no value to anything that cannot be translated into dollars , and that demands perpetual growth in order to support a return on investments.


Does Life Extension Contribute to Overpopulation?

Well yes, of course it does.  Human history since the advent of agriculture has been a quest to tame the environment, to substitute predictable domestication for nature’s wild ride.  We have done this to avoid death and the risk of death.

But only since 1840 has there been any  significant advance in human life expectancy .   Our animal nature has responded reliably, compensating with a lower birth rate that not even fundamentalist religious ideologies have been able to hold back.  But between lowered death rates and lowered birth rates there has been a gap of 30-40 years, leading to a dramatic growth in the human population.   Aldous Huxley recognized this pattern as early as 1956. “What we’ve done is ‘death control’ without balancing this with birth control at the other end….”

The gap between falling death rates and falling birth rates produces a population surge.

Currently, Africa is the last continent where technology is finally moving in to increase life expectancy, and the African birth rate is coming down, but not fast enough to avoid devastating population increases. Over the next 30 years, the population of Africa is expected to double from 1.1 billion to 2.4 billion, a larger absolute increase than the rest of the world put together.

Life span in 1840 was about 40 years in the world-leading European countries. In 2015 it was 83 in Japan and Scandinavia, the present world leaders.  And indeed, the increase has been quite steady and gradual, so that “one year for every four” is an accurate characterization.  For the first 120 years, increased life span was a story of early deaths prevented.  Before about 1970, all this progress in life expectancy was achieved by preventing people from dying young, benefits reaped from antibiotics, hygiene, and workplace safety. But since then, a remarkable thing has happened: the maximum human life span has risen, and continues to rise at an accelerating pace (as recounted by Oeppen and Vaupel). What is more, people in their seventies and eighties are healthier today than ever before. Although there are dramatically more seniors in the population, the proportion of the population in assisted living and other dependent care situations is not rising. This is just what we wanted–we are staying active and healthy longer, retiring later, delaying the ravages of old age and “compressing morbidity” of late life into a shorter endgame.

Rising life expectancy over 160 years (from Oeppen & Vaupel)

Rising life expectancy over 160 years (from Oeppen & Vaupel)


Gratifying for the individual–treacherous for the collective

World population at 7.3 billion is about ten times what it was in 1800.  A tenfold increase over 200 years is a good run, but it’s not unusual in the context of the biosphere’s history.  Far from it.  Bacterial populations routinely expand by a factor of a million.  Insect populations can boom and crash.  There are many examples even of large animal populations that have grown far faster than Man.

But other population increases have been local, while the rise of mankind has been all over the planet.  We are now a global population, adapted to living in deserts and jungles, snow-capped mountains and forests and fields.  We mow them all down, or burn them, or pave them over.  Man has put many other predators out of business, from mastodons and sabre-tooth tigers to moas to a slew of toads and salamanders in the present age.  We inhabit every corner of the earth and have wrought just as much devastation on the seas–perhaps more.  Technology has enabled us to dominate such a wide range of other species, and it has made human beings a uniquely devastating competitor.



Will we Destroy all Life on Earth?

Don’t give yourself airs.

Eradicate Gaia? Life is bigger and more robust than anything we are able to disrupt. No, the threat is not to Gaia but to ourselves. Life will eventually roar back, more diverse, more wondrously inventive than ever. But recovery from a mass extinction requires, typically, a few tens of millions of years. That’s nothing for Gaia, but for our grandchildren, 30 million years may try their patience.

There is life in boiling hot sulfur pits and life on the pitch black ocean floor, thriving under pressure that would crush a SCUBA tank, and life embedded in dry rock, equally deep under the land, living on who-knows-what. There are spores that were trapped in salt deposits 250 million years ago, recovered by scientists and brought back to life in the laboratory. To eliminate all life on earth is far beyond humanity’s destructive power for the foreseeable future.

But can we imperil the ecosystem that sustains human life? Quite possibly we can.

We may imagine the worst case scenario is that we destroy all of nature, lose all biodiversity and turn the earth into a vast farm to feed 20 or 30 billion humans.  But it’s a good bet that this kind of world cannot be, and it is certain that we don’t know how to create it.  Ecosystems are complicated and interdependent.  From bees to bacteria, our farms and our pastures and livestock all sit atop ecosystems that we do not  fully  understand.  Already, we are washing into the sea each decade topsoil that took 1,000 years to create .  Farmers rent hives of pollinating bees, and the beekeepers are keeping them alive with increasing difficulty .  For nitrogen-fixing bacteria, we have substituted saltpeter that we mine from the ground until there is no more of it left to mine.

Still life with steamshovel

Still life with steamshovel

Factory farming and antibiotics are two of mankind’s most successful and heavy-handed biological interventions.  Each has worked spectacularly well for a few decades, and we have perhaps a few decades more before each will as spectacularly fail.  We have that much time to create more sustainable replacements.

No, a world of monoculture to feed humans is not a viable world.  We are animals.  From an ecosystem we derived, and, for the foreseeable future, on a natural ecosystem we will continue to depend.  We are not nearly smart enough to build an artificial ecosystem to support human monoculture.  In all likelihood, the end of natural ecology would be the end of humanity.

Poets bemoan the loss of our spiritual connection to nature.  Meanwhile, ecologists warn us that we are starving more than our spirits.  We can’t engineer our way out of this.  We don’t know how.  We can’t understand or model ecosystems, so we have no idea how to move them in a given direction, even if humanity had the collective will to do so.  If we destroy the ecosystem we have, we will have to wait for nature to take her course, and the wait is likely to be tens of millions of years.


Libertarian ethic

Many of my colleagues in the life extension community lean to libertarianism, and in some ways I am with them.  I am frightened by our disappearing Bill of Rights, corporate takeover of the Free Press, exceptions to habeas corpus, wholesale domestic surveillance–and all this in service to perpetual war which most Americans want no part of.

But overpopulation and ecological collapse are problems that cannot be addressed individually.  China realized decades ago that we cannot allow each family to decide how many children they wish to have.  Still less can we condone men who impregnate women and walk away; and worst are the institutions that seek to preserve the morals of other people’s children by denying them knowledge of basic reproductive biology.

Gathered to see the Pope

Gathered to see the Pope

We will have to find ways to come together.  The good news is that polls show consistently that people are aware of the threat and willing to put aside their own (short-term) economic interest to address it.  (This despite concerted efforts to downplay the issue in the media.)  The bad news is that present political structures will not address the problem.  Our existing political order is, in fact, a big part of the problem.  Politics is dominated by capitalist megacorporations that have their own agenda, and preserving the ecological foundation of human life is not part of it.  Subversion of democracy by capitalism may have taken root in America and West Europe, but it is now a global blight.

We must work around government, the corporate media, the megacorporations and the whole capitalist economy.  We must come together to consolidate and act on an existing consensus for

  • A rapid transition to renewable energy
  • Policies to encourage smaller families
  • Limits to fishing, among other measures to protect the oceans
  • Protections for natural habitats on land

I invite your thoughts and ideas about how to do this.

The more dramatic images in this column were taken from the book Overdevelopment, Overpopulation, Overshoot , published this year and available free online or for purchase in hard copy.

* Aging genes or the equivalent, combinations and epigenetic networks that work to ensure that our bodies weaken and ultimately self-destruct over time.

** Since they are hermaphrodites, each worm can breed without a partner, and so needs only 2 surviving offspring rather than 4 to double its population.

We Know Nothing about Longevity Drug Interactions

Years ago, I worked for an energy conservation priest whose motto was, “anything worth doing is worth doing poorly.”  We were training unemployed young people to install fuel-efficient furnaces in the homes of people who couldn’t afford heat.  My boss’s point was that the new furnaces were so much more efficient than the old that even if they were installed sloppily they would save enough fuel to turn a profit.  

If you focus on the big picture and get it right, the details don’t matter so much.

In tests with mice, a dozen or so different treatments have been found to lead to modest life extension.  The most urgent need at present is to begin studying how these treatments work in combination.  But there are too many combinations, and tests with mice are expensive.  That’s why it makes sense to do a quick-and-dirty job testing all combinations at once.

(This is a research proposal, the germ of an academic publication that I have been working on in recent months, and plan to submit to a journal and to the NIA next year.  I am experimenting with the idea of publishing it first as a blog.)

I take about a dozen different pills for longevity.  There is some evidence behind each of them, but what we really don’t know is how they interact.  It would be nice to think that their benefits simply add, so that if one pill produces a 10% average increase in life span, then 10 pills increase life span 100%.

Fat chance.

Some of them are ineffectual, of course.  But for the ones that offer a benefit, most of the benefits are probably redundant.  (When different treatments work via the same pathway, we can’t expect that two together work any better than either one of them separately.)  A few may mutually interfere.  But there also may be a few magic combinations that synergize positively.   If they work via pathways that are substantially independent, we might hope that the life extension from the two together might be equal or even greater than the sum of the benefits separately.

Most of the life extension drugs that we have target a single pathway: they work through the insulin metabolism.  The remainder work to suppress inflammation, or re-energize mitochondria, or lengthen telomeres, or reduce TOR signaling.


Tests in Mice and Rats

There are many ways to extend life span in worms and even in flies.  Some of these have also been tested in rodents, and they don’t pass muster.  I have argued that we should concentrate on mammals.  Even though they are much slower and more expensive, longevity studies in mammals are a far better guide to what might work in humans.  When a drug is found that extends life span in mice, there is a good chance it will also work for people (though percentage increase of our 80-year life spans is likely to be smaller than the corresponding percentage in the 2-year life span of a mouse).

Caloric restriction and exercise work consistently to increase average life span in mice.  Several genetic modifications are known to work, too.  The drug and supplement treatments for which there is best evidence include:

The many drugs that show promise but need further testing include

    • Deprenyl
    • ALK5 inhibitor
    • Epitalon/Epithalamin
    • MitoQ/SkQ
    • Beta Lapachone (Pao d’Arco)
    • Spermidine
    • Berberine
    • Dinh lang (Policias fruticosum)
    • Pterostilbene
    • Gynostemma pentaphyllum (jiao gulan)
    • N-Acetyl Cysteine (NAC)
    • Ashwagandha
    • Turmeric/curcumin
    • C60
    • Oxytocin (not oral)
    • J147
    • NR and NAD precursors

(Most of these were discussed briefly in a column I posted in September, and in other past columns.)

Almost no work has been done with combinations of longevity treatments.  In 2013, Steve Spindler’s lab published a study based on eight different commercial formulas of vitamins and supplements.  Their data were beautiful–and the survival curves for each of the eight fell exactly along the survival curve of the control group.  I have heard that the NIA’s Interventions Testing Program (ITP) has tested rapamycin in combination with metformin, with successful results (to be published next year).

In a rational world, some of the billions of dollars that go into “me too” drug development and chemotherapy trials by Big Pharma would be diverted to test all of the above compounds, alone and in combination.  But in the branch of the multiverse where you and I live, this will not happen in 2016.  Hence “quick and dirty” (= cheap) alternatives look attractive.


The plan is to screen for combinations of drugs that offer dramatic life extension in mice, using the minimum number of mice to test the maximum number of combinations.  Standard practice is to use 30-80 mice for each test in order to get a clean survival curve.  The innovation I am offering is to use just a few mice for each combination of treatments so that more combinations can be tested, albeit less precisely.  How many mice do we really need to be reasonably sure of not missing an outstanding combination of treatments?

I have been modeling the situation with computer-generated data, testing different statistical methods to see which works best, and how many mice are needed in order to be reasonably certain of not missing a great combination.  My definition of a great combination is that it extends life span in excess of 50%.  The test I propose will not be capable of distinguishing “which is better” among the rank-and-file of many treatments and combinations.  However, there will be enough statistical power to identify the really hot performers, which are of most interest to us.

Specifically, I have modeled experiments based on 15 different treatments.  In the most practical and successful of the methods, I combine all different triples among 15 treatments (there are 455 of them, from a well-known statistics formula Combin(15,3)).  I’ve assigned 3 mice to each triplet of combinations for a total of 1365 mice.

I use statistics to tease apart the effects of different treatments and different combinations.  Analysis is based on multivariate regression, but since MVR works best with just 2 or 3 variables at a time, I have been experimenting with the details of an analysis program that looks at 1 to 3 variables at a time, then does a smart search for “nearby” criteria that might do a bit better.


The Model

I generate sample data for 1365 mice, based on each mouse having a randomly life span drawn from a bell-shaped curve.  The center of the bell-shaped curve depends on what treatments the mouse is getting.  (This is the “right answer” that the analysis is trying to find.)  The width of the bell-shaped curve is between 20 and 25% of the average, because this is the scatter that the better mouse laboratories find in their life span data.

To generate the means, I assume that each treatment offers some random amount of life extension, also drawn from a bell-shaped curve.  I assume that the treatments interact in pairs and that the interactions are mostly destructive, but some of the treatment pairs interact synergistically.

For example, if a mouse is receiving treatments A, B and C, then I assume its mean predicted life span is the sum of A and B and C separately plus the three interactions (A,B), (B,C) and (A,C).  (To simplify, I have assumed there is no separate term for a purely three-way interaction of (A,B,C).)   This is the mean life span for that one mouse, and that mouse is assigned a life span that is a random number centered on that mean.

Since we are most interested in combinations that yield large benefit, I have adjusted the parameters so there is always at least one triple combination that (on average) has benefit of >50% life span extension.


Preliminary results

      • About 40% of the time, I hit the nail on the head and identify the best triple and the best pair.
      • About 85% of the time, the best triple is among the top 3 generated by my analysis
      • About 95% of the time, the best triple is among the top 6 generated by my analysis


Tentative conclusion

I think this looks promising.  I am working with Edouard Debonneuil, who will check my calculations and contribute some of his own.  Edouard has more experience than I have both in the practical business of managing a lab experiment and in the practical business of finding funding and sponsors.

I believe that using about 1400 mice in an experiment lasting about 3 years, we should be able to evaluate all combinations of 15 separate life extension treatments, and narrow the field to 6 candidate triples that show offer life extension in excess of 50%, and thus show promise for further testing.


…and in the Real World

The program I have outlined could be undertaken for less than the cost of testing the 15 separate treatments using traditional methodology, and I think what we would learn from the combinations protocol could be a great deal more useful.  The total cost might be $1 to $3 million, depending mostly on where the work is done.

The biggest risk is that the high-benefit “magical” synergistic combinations that this program is designed to look for simply don’t exist.  If they do exist and can be found, the public health impact is likely to be enormous.

But in today’s economy, who will fund this work?

National Institute for Aging in Baltimore has the Interventions Testing Program (ITP), funded at $4.7 million.  Because they have high overhead and because they fund elite institutions with American salaries and because they repeat each experiment in triplicate, they can test only 1 to 2 compounds a year.  There is no activity from pharmaceutical companies, except for the few compounds that can be patented.  Some private foundations and crowd-funding groups have stepped forward to try to fill the void.  The Glenn Foundation has cut back.  The SENS Foundation is spread pretty thin.  I’ve recently connected with the Major Mouse Testing Program (MMTP) of the International Longevity Alliance.