An Outline of Progress in Longevity Science

Here is a short email that I received yesterday:

I have been reading about [longevity research] for a week now and I was just wondering if you were making progress on this? I read some people think aging can be cured in 2029 could that actually happen?

So today, I'll scribe a brief perspective on recent progress in longevity science. I should preface this by noting that it is probably best to think of the life science and medical research community as an array of largely independent groups and factions, some large, some small. While there is a lot of cross-pollination in their work, they move at different rates towards different goals in medicine and biotechnology, and those goals are of varying degrees of usefulness when it comes to allowing humans to live longer, healthy lives. So I'll note what I see as the areas worthy of particular notice, and omit many other areas, some of which are still important or interesting in their own right:

Early Work on Rejuvenation Biotechnology

The SENS Foundation manages a small-in-budget but large-in-scope research project, and networks with a range of allied scientific groups. The vision is to build true rejuvenation biotechnology, an implementation of the detailed SENS vision for how to repair and reverse the causes of aging. The Foundation is as much about persuading more of the scientific community to undertake aspects of this work as they are about running their own research and development center.

Progress here over the past decade is measured by the fact that the SENS Foundation didn't exist as anything more than the beginnings of an idea back then, in a research community that was far more hostile towards engineered longevity than at present. The Foundation is now an actual entity, with many allies in the aging research community and a million-dollar yearly research budget provided by philanthropic donors. The scientific community itself is now open to work on engineering human longevity, and that is largely due to the efforts of the SENS Foundation principals, supporters, and allies.

You can't change the world with a million dollar budget, alas, but this is just the start of what will hopefully blossom to become the dominant form of aging research - work targeted on the reversal of aging, rather than merely understanding it or slowing it down.

Regenerative Medicine and Tissue Engineering

Stem cell medicine of all forms is growing very rapidly, a worldwide industry that is producing tangible results at a very fast pace: engineering patient-matched tissues and organs, controlling cells to spur regeneration, understanding why stem cells decline with age, and much more. This is a massive research and development community, enormously well funded, enjoying widespread public support, and still growing.

It is not unreasonable to expect that people in middle age today will be able to have lab-grown organs made to order when it comes time to need them, twenty years from now. More importantly, we can also fairly confidently expect to see major advances in reversing stem cell decline with age over that same time frame. Most of the market for stem cell based medicine involves elderly patients, and understanding how to revive stem cell populations in the old will be a necessary part of implementing new therapies. The financial incentives are strong here, and are already being acted on.

Harnessing the Immune System

At the highest level, we can think of regenerative medicine as the inevitable outgrowth of new tools and new understanding that allow stem cells to be manipulated. Control the cells that build tissue, and you can control healing, regeneration, and the ability to maintain tissues in working condition over time. But this very same technology and knowledge also enables immunology and immune therapies: understanding and manipulating the immune system, which is at root just another collection of specialized cells.

The immune system serves many vital purposes in the body, and decays in characteristic ways with advancing age. Many of the frailties of aging are caused by or exacerbated by the progressive failure of the immune system to do its job - not just protecting against pathogens, but policing the cells of the body to destroy those that cause harm.

Just as regenerative medicine will ascend to building new organs over the next few decades, so too will advances in immunology lead to control over the immune system, including restoration from age-related decline. These are closely related fields, and progress in both is enabled by the same underlying biotechnologies. In recent years, we have already seen the first demonstrations of the ability to reprogram, reset, and reverse some of the age-related declines in immune function. At the same time, many new therapies are under development based on manipulation of the immune system: to destroy cancers, repair autoimmune diseases, and so forth.

Calorie Restriction Research and Mimetics

A great deal of resources are pouring into understanding the metabolism of longevity, and one part of that is the quest to understand and replicate the effects of calorie restriction on health and life span. What probably amounts to a few billion dollars over the past ten years have gone into advancing this field, which in that time has grown from a tiny minority interest in a few labs to a large and growing concern that, despite little to show for the investment yet other than knowledge, doesn't look to be slowing down any time soon.

Progress here can probably best be measured in our increased understanding of exactly how metabolism can shift into states that boost health and life span in most species. Increasing numbers of potential drug compounds have been identified that somewhat recapitulate the beneficial effects of eating less, but it seems unlikely that anything other than a carefully designed small molecule drug with very specific biochemical targets will prove to be a true calorie restriction mimetic. As of yet it seems that too little is known to build such a thing, but there is a fairly good idea as which mechanisms it would affect in order to achieve its ends.

The Genetics of Longevity

A great deal more work is taking place on the genetics and epigenetics of longevity than was the case a decade ago. This is a growth field, both for human studies that try to pick apart genetic contributions that lead to long-lived families, and for comparison studies between long-lived and short-lived species, where researchers search out distinctive differences that might explain how large variations in life span come about.

In humans, we can now be more confident that there are many genetic contributions to longevity, varying widely by population, and few if any stand out as large and obvious targets for drug development. Meanwhile the attention paid to long-lived species such as naked mole-rats is producing data that steers the attention of other research communities to the most important determinants of longevity - our mitochondria and their resistance to damage, for example.

The Bottom Line

The bottom line is that the research community and state of the field today is very different from that of even a mere ten years ago. This is a time of rapid change and progress: far more is known and far more impressive feats of medicine can be performed in the lab and the clinic. There is every reason to believe that ten years from now we'll be able to say the same thing. Costs in biotechnology and life science research are falling rapidly, and with that trend more research can be accomplished in each new year.

That said, however, the only way that we'll see significant inroads into the defeat of aging by 2029 is for the SENS Foundation and its attendant research community to undergo the same sort of growth over the next decade as has been exhibited in recent years by regenerative medicine, calorie restriction research, or study of the genetics of longevity. A growth to billions in funding and thousands of researchers, in other words. It will require at least that and a decade of time in order to have a 50/50 shot at reversing aging in old mice in the lab - which is to say something that can make them live at least twice as long as they otherwise would have done.

Of all the items covered in this post, only SENS provides a path towards achieving this end. Even regenerative medicine and complete control over stem cells can't offer the possibility of reversing aging in and of itself - it is only the way to reverse one component of aging, the decline of tissue maintenance and frailty that results from stem cells shutting down. You will still get nailed by your own mitochondria and the build up of metabolic byproducts even if your stem cells are perfectly restored.

So to answer the original question posed in the email, no, there is no plausible road to the defeat of aging by 2029. But there is a plausible road to the first laboratory demonstrations of real, meaningful, but partial age reversal by then, ways to actually repair the root biological causes of aging rather than just slow it down. Whether that happens or not depends absolutely on funding - there are more than enough scientists and research groups out there who would work on the SENS vision for rejuvenation biotechnology if given a budget, but as of yet not enough funding sources to make it a reality.

Comments

It would seem that things have all but ground to a halt during the past few years.
Things may even be going backwards in the USA. The effect of obesity is becoming an epic event.
The resession has put health on the back burner for many. We seem to have lost a decade.
At 57 that is not such a good thing. I wish the original plan of treating the major issues as engineering problems , would be taken by a new breed of health tech people. Maybe bio hackers wi prevail and finally get michochondria to signal which ones are defective. Heck it's just ATP production and a little brain garbage removal. Sure hope some kid just does it.
Should the efforts be centered in Asia ? No FDA to get in the way ?
Any way I'm just quite disappointed with this past decade. Fingers crossed

Posted by: Tim Davies at August 30th, 2012 5:43 PM

Millions are being poured into anti-aging science and regenerative medicine - most orgs are public-funded institutions. It's definitely getting the attention of Big Pharma, too. So, I'm not sure what is meant by things grinding to a halt...? I read every day how new breakthroughs are being researched. It's mostly being paid for by tax money, so there are loud cries from the anti-tax zealots who don't want to fund experimental research no matter what. A lot of wild sounding advances are being made in Russia, with science fiction-ey sounding events like growing human limbs in the lab, etc. There's no FDA there, either, but do you really want to go along with all the unregulated experimentation? Human experimentation, I'd have to assume?

Posted by: Jeffrey Frentzen at August 31st, 2012 2:21 PM

I don't think heavy regulation is a good idea with radical life extension research. If there is sufficient peer review and legitimate research being done, the FDA should not press to slow the development and testing of whatever drugs may come about.
What 'wild' advances they advertise are usually projections of current research. (seriously... all I hear these days are projections.. outlooks.. future directions.. etc..). Either that, or they are way too expensive for practical use. So on the -application- perspective, technological advancement seems reallllyy slow (as if it has grinded to a halt).
And although we hear about new developments quite often (for anti aging), there still seems to be no -GENERAL- progress. Sure, a drug/discovery/technique pops up here and there, but not many people have attempted to connect the dots. Even so, the pace of these basic discoveries is much slower than it could have been if given legitimate funding.... (comparable with the amount we waste on war for example..).

Maybe time is just moving too slowly for me... but I check Nature, ACS, RSC, and a few other sites almost every day... just to facepalm at how slow the tech is moving. On the bright side, it makes me work harder so that I may one day contribute to the fields.

Posted by: Yunlong Yang at August 31st, 2012 8:18 PM

There is no money shortage.

The mistake in life is to constantly look for what you don't have. The excuse that something is not available, so we can't do things, has kept humans 100,000 years behind in technology evolution. Cavemen and spacemen are the same people. Identical apart from the ideas they have. Tske Ugg and teach him science and you get Buzz Aldrin.

We are not, and never will be, short of anything, apart from ideas. There is no shortage of any resources. Energy and material are totally without limit. You generate energy from mass, mass is material, universe mass has no known limit. Recessions are mass histeria, causing and caused by failure to generate ideas. Ideas are wealth, there is no money reality, no land limit, no resource limit, mercantilism is gone.

Even on this planet, the stories spread about resource use and population is most limiting. All the planetary resources the Earth started with are still here and not going anywhere, no matter what we do. In fact (despite the loss of the odd spacecraft and infra red emissions) solar insolation and meteor strikes increase planet resources day by day. Nonthing gets used, only moved or transformed. It's all still here. You can use stuff as fast as you like, it never goes away. And even ignoring nuclear mass transformations, solar insolation is many thousands of times the energy requirement for everything we can think of.

As to population concerns. Broad group in 6 months can build a self contained 30,000 person building on 150m x 150m plot of land or floating platform. That equates to a population of over a Trillion on the land alone, with room to spare.

Unlike biological evolution. There is no essential time delay either, no inherrent rate of technological evolution. Ideas can be instant. Technology can change for you personally at 1000 years a day. A Masai warrior need not wait 1000 years to use a mobile phone, he can call his mum today.

So generate ideas much much faster. Use the internet, use systems, use people, use competitions, use networks. Soon we will use intelligent machines, it is not a subject for debate, it will happen come what may, get with the program. We just need a bridge till then. Construct, assess, design. Move 1000 years a day. Take no excuses. Don't be a cavemen.

Do not wait for money. You'll die first.

Waldo Hitcher

Posted by: Waldo Hitcher at September 1st, 2012 12:04 AM

There Is money shortage.

If funding doesn't affect scientific advancement very much then scientists wouldn't be wasting their time asking for it.

Sure, without it we will still get there...eventually.
It's all about the amount of time it takes us to get there. (which in this case should be asap).

Indeed, science can solve our current 'limiting resource' crisis. If given enough attention and funding, we probably would have solved much of it already.

Posted by: Yunlong Yang at September 1st, 2012 5:59 PM

I want to believe and rally what Waldo says. At the least, it's a damn good pep-talk and motivator, which decreases barriers. It's just that ideas and knowledge build on each other and depend on billions and trillions of aligned people, brain cells, and world-wide resources. The cave man with caveman resources couldn't build a rocket ship, let alone mission control, even over a lifetime. The Masai can't gather his tribes men together and with their existing skillsets, construct cell towers and hundreds of years and tens of thousands of lifetimes worth of scientific progress that built to the point where we can do what we do today with vast cellular systems.

Can we think of, ponder and imagine these ideas with more freedom and with less roadblocks? Sure. Can we develop breakthrough scientic research, findings, and results overnight? Heck no. We have to build on what we know, synthesize data from other ongoing and past science, and bit by bit build the skyscraper that is needed. All at the same time, everyone involved in the progress, needs to live their life's. They need to eat and survive and be happy. This all costs resources and it takes time.

When you are talking about one person or small groups, sure, microcosms shouldn't allow money to hamper their progress. When you are talking macro-level progress - stuff that takes large portions of the human race to achieve - you need resources. If we can focus more resources towards a goal, it has more chances of getting completed, and in a quicker time frame.

We may not be limited in the sense of maximum amounts of resources. We are limited by human information sharing, interactions, process-based and physical progress.... At least for now - we all know that that limit is decreasing by the day.

Don't wait for money? If scientists and technologists around the world don't find money, heh, they will die of starvation.

Posted by: Nick Yeates at September 2nd, 2012 12:39 AM
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