When I am Eighty-Five

I will be 85 somewhere in the mid 2050s. It seems like a mirage, an impossible thing, but the future eventually arrives regardless of whatever you or I might think about it. We all have a vision of what it is to be 85 today, informed by our interactions with elder family members, if nothing else. People at that age are greatly impacted by aging. They falter, their minds are often slowed. They are physically weak, in need of aid. Perhaps that is why we find it hard to put ourselves into that position; it isn't a pleasant topic to think about. Four decades out into the future may as well be a science fiction novel, a far away land, a tale told to children, for all the influence it has on our present considerations. There is no weight to it.

When I am 85, there have been next to no senescent cells in my body for going on thirty years. I bear only a small fraction of the inflammatory burden of older people of past generations. I paid for the products of companies descended from Oisin Biotechnologies and Unity Biotechnology, every few years wiping away the accumulation of senescent cells, each new approach more effective than the last. Eventually, I took one of the permanent gene therapy options, made possible by biochemical discrimination between short-term beneficial senescence and long-term harmful senescence, and then there was little need for ongoing treatments. Artificial DNA machinery floats in every cell, a backup for the normal mechanisms of apoptosis, triggered by lingering senescence.

When I am 85, the senolytic DNA machinery are far from the only addition to my cells. I underwent a half dozen gene therapies over the years. I picked the most useful of the many more that were available, starting once the price fell into the affordable-but-painful range, after the initial frenzy of high-cost treatments subsided into business as usual. My cholesterol transport system is enhanced to attack atherosclerotic lesions, my muscle maintenance and neurogenesis operate at levels far above what was once a normal range for my age, and my mitochondria are both enhanced in operation and well-protected against damage by additional copies of mitochondrial genes backed up elsewhere in the cell. Some of these additions were rendered moot by later advances in medicine, but they get the job done.

When I am 85, my thymus is as active as that of a 10-year-old child. Gene and cell therapies were applied over the past few decades, and as a result my immune system is well gardened, in good shape. A combination of replacement hematopoietic stem cells, applied once a decade, the enhanced thymus, and periodic targeted destruction of problem immune cells keeps at bay most of the age-related decline in immune function, most of the growth in inflammation. The downside is that age-related autoimmunity has now become a whole lot more complex when it does occur, but even that can be dealt with by destroying and recreating the immune system. By the 2030s this was a day-long procedure with little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis is curable, preventable, and reversable, and that has been the case for a few decades. There are five or six different viable approaches in the marketplace, all of which basically work. I used several of their predecessors back in the day, as well. Most people in the wealthier parts of the world have arteries nearly free from the buildup of fat and calcification. Cardiovascular disease with age now has a very different character, focused more failure of tissue maintenance and muscle strength and the remaining small portions of hypertension that are still problematic for some individuals. But that too can be effectively postponed through a variety of regenerative therapies.

When I am 85, there is an insignificant level of cross-linking in most of my tissues, as was the case since my early 60s. My skin has the old-young look of someone who went a fair way down the path before being rescued. Not that I care much about that - I'm much more interested in the state of my blood vessels, the degree to which they are stiff and dysfunctional. That is why removal of cross-links is valuable. That is the reason to keep on taking the yearly treatments of cross-link breakers, or undergo one of the permanent gene therapies to have your cells produce protective enzymes as needed.

When I am 85, I have a three decade patchwork history of treatments to partially clear this form of amyloid or that component of lipofuscin. Modified enzymes are delivered here, a gene therapy applied there. I will not suffer Alzheimer's disease. I will not suffer any of the common forms of amyloidosis that degrade heart muscle performance or disrupt function in other organs. The potential for such conditions is controlled, shut down with the removal of the protein aggregates that cause cellular dysfunction. There is such a breadth of molecular waste, however: while the important ones are addressed, plenty more remain. This is one of the continuing serious impacts to the health of older individuals, and a highly active area of research and development.

When I am 85, I am the experienced veteran of several potentially serious incidences of cancer, all of which were identified early and eradicated by a targeted therapy that produced minimal side-effects. The therapies evolve rapidly over the years: a bewildering range of hyper-efficient immunotherapies, as well as treatments that sabotage telomere lengthening or other commonalities shared by all cancer cells. They were outpatient procedures, simple and quick, with a few follow-up visits, so routine that they obscured the point that I would be dead several times over without them. The individual rejuvenation technologies I availed myself of over the years were narrowly focused, not perfect, and not available as early as I would have liked. Cancer is an inevitable side-effect of decades of a mix of greater tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be in the 2050s? No. It is next to impossible to say how the differences noted above will perform in the real world. They are all on the near horizon, however. The major causes of age-related death today will be largely controlled and cured in the 2050s, at least for those in wealthier regions. If you are in your 40s today, and fortunate enough to live in one of those wealthier region, then it is a given that you will not die from Alzheimer's disease. You will not suffer from other common age-related amyloidosis conditions. Atherosclerosis will be reliably controlled before it might kill you. Inflammatory conditions of aging will be a shadow of what they once were, because of senolytic therapies presently under development. Your immune system will be restored and bolstered. The stem cells in at least your bone marrow and muscles will be periodically augmented. The cross-links that cause stiffening of tissues will be removed. Scores of other issues in aging process, both large and small, will have useful solutions available in the broader medical marketplace. We will all live longer and in better health as a result, but no-one will be able to say for just how long until this all is tried.

Comments

Thanks for the article. Very inspiring. Let's make this future a reality!

Posted by: Antonio at May 29th, 2018 3:25 PM

And here we have Reason showing his optimistic side! I like it.

Same boat as you Reason. In 2055 I'll be 85 exactly.

Maybe we will hit LEV, maybe not. At least our quality of life for Gen X and beyond will be much improved. Maybe Kevin Smith will get around to Clerks 8. It would be apt if Randal and Dante are still working the convenience store :)

Its also highly likely we will have a fair bit of life extension as well.

I'm bookmarking this entry so I can come back to it every so often. I'll be raising a glass to this post tonight with the wife.

Posted by: Mark Borbely at May 29th, 2018 5:31 PM

@Reason, I believe in 2050 the young appearance will be the least problem, engineers will be able easely grow and transplant new skin for your face.

Posted by: Ariel at May 29th, 2018 6:06 PM

I have to agree with Ariel, by 2050 I think it likely that treatment of the external signs of aging will be highly advanced. Much as serious scientists may hate it, there's already a huge cosmetic industry treating the skin - creams, peels, laser treatments etc and you'd have to think that when treatments that really work appear on the horizon the potential for profit will generate an avalanche of funding.

Seeing is believing, and people look in the mirror every day. It's one thing to get your thymus regenerated and know that you are now less likely to get cancer thanks to a youthful immune system. It's another thing to look in the mirror and see a 40 year old face looking back at you when you are 60.

There's enormous, positive, daily feedback from a truly effective treatment to rejuvenate the skin, which means that the first treatment that manages to take 3 years off your apparent age (with acceptable pain/side effects) is likely to be wildly successful, and every major drug/cosmetics company will have to fund their own version, and the 2nd & 3rd generation follow-ups, simply to avoid being left out. After a couple of decades of this, aging treatments aimed at skin and hair are likely to be years ahead of the internal treatments due to the funding gap.

I don't think this is necessarily a bad thing. It's easier to verify the effects of external treatments, it's not as scary as something happening deep inside you, the pay off is obvious and visible, so people will be more willing to take the plunge and undergo treatment. As effective external, cosmetic treatments become widespread it normalizes rejuvenation as a procedure and a goal. The obvious objection to it is "you only look young on the outside, you're still old on the inside" and the obvious rebuttal is "yes, we need to work on rejuvenating the inside too".

Just as people may look in the mirror and see wrinkled skin and thinning hair and feel discouraged about their mortality, so they may look in the mirror at rejuvenated skin and hair and believe that full rejuvenation is possible. And if all their friends are updating their Facebook profiles with pictures that look ten years younger, then we may reach the point where calls for increased longevity funding become commonplace and mainstream, and biotech companies allocate billions to it each year.

Posted by: Chris at May 29th, 2018 8:29 PM

Hi Reason,
Having multiple cancers by 85 is not very likely. Even now days it is rare to have more than one and yet the life expectancy is close to 80. If the senolitics are available within 10 years they will reduce the cancer incidence significantly. I will take your word for the thimus boosting as you are one of the few experts in that.

However, you are conservative on your estimate. The scientific and medical discoveries will only multiple with years. The is a good chance that they will be some form of nano-microbiology machines. Probably in the form of wetware repurposed from bacteria or cells. Organ printing and transplantation will be routine and often done for body modification purposes like today's piercing and tattoos. And this is the conservative view.

The moment the first anti aging therapies are proven to work in humans the investors floodgates will open and all kind of anti-aging research will be financed( just look at how much money is poor in block chain and coins). Artificial intelligence, nanotechnology and biology will converge to give improvement surpassing CRISP application every few years. Which and where I cannot tell. In fact the most critical years are the next decade and a half. The rest would be history. From our selfish POV those years will make the difference between reaching the LEV or dying just a few years short of it.

I subscribe to the b freeelieve that there is a form of progress determinism in the sense that a discovery happens when the time is right and if it happens earlier there will be little application, a.k.a "before one's time"
That's why the SENS progress was too slow over the last 20 years. Of course if you poor enough resouces you cold speed (or slow down if you fight it) the progress in a given domain.

Now it's the time when many enabling factors converge. One is the change in perception of the biological community due to promotion done by SENS and friends. Another is the improvements in the genetic tools for analysis and modification. Then there are bio printers and automation tools. And the power of more sharing trought internet. A startup could setup a shop in a cheap location or friendly regulations and "telecommute" to control the experiments

Posted by: Cuberat at May 29th, 2018 9:12 PM

If only the people in their 40s, 30s, and 20s today who are overweight and obese and will get type 2 diabetes knew this, they'd definitely be more motivated to lose the excess weight.

Posted by: Jim at May 30th, 2018 12:05 AM

What about stem cells? Why not just regenerate portions of the body that need it? What about breathalyzer tests that detect cancer very quickly after its onset?

Posted by: sanman at May 30th, 2018 12:47 AM

I am hopeful we will have some significant medical rejuvenation treatment available by 2030. Minimally, at least rid our bodies of senescent cells, if not one or two additional treatments.

Hopefully the speed of extra treatments will increase with time, especially once the public sees what is happening with senescent cells. I guess one can hope, especially with convergence of many technologies such as nano, AI, robotics, CRISPER, maturing of Oisin and Unity Biotechnologies, and many others.

Posted by: Robert at May 30th, 2018 1:57 AM

@Jim
>If only the people in their 40s, 30s, and 20s today who are overweight and obese and will get type 2 diabetes knew this, they'd definitely be more motivated to lose the excess weight.

I on my end have lost about 20 pounds and I am working on it. A friend of mine said that I look like I have "lost 20 years", which is not the case but I do look younger and my sporadic fasting seems to reduce the skin cross-linking
, At least visually impress the skin elasticity..

Posted by: Cuberat at May 30th, 2018 5:16 AM

This is the kind of writing you do best.

This is how you bend reality and make it happen your way.

Posted by: arren brandt at May 30th, 2018 5:16 AM

Desperate attempt of a fragile meat human not to be assimilated.

Posted by: Peter Choczynski at May 30th, 2018 10:47 AM

I hope you are right

Posted by: JohnD at May 30th, 2018 11:46 AM

@Chris, you make a very common mistake -- you assume that appearance problems are very different from health problem. They are not -- in fact "appearance" is part of your health, because your skin, your hair, your muscles are part of your body. That is why you cannot meaningfuly rejuvenate your appearance alone, because one is the mirror of your health. You need to fix all 7 types of damage, only one of them -- cell therapy -- is very tissue specific. So there will be no and can be no any much contrast between your appearance and your health!

Posted by: Ariel at May 30th, 2018 2:37 PM

As far as skin aging goes, there already are some really weird treatments that work well, and some of them have a fairly long history of use. One is simple occlusion of the skin with a barrier such as silicon tape (the kind used for scar treatment) or paper-backed adhesive ('Frownies'). Another is microcurrent. Urea is a topical that is said to be useful for desquamation, but it appears to have other activities since it can get rid of spider veins and reduce finger-nail ridging. It is strange that mechanisms of these treatments haven't been researched much or at all since there are apparently some biologically interesting things going on.
At any rate, being healthy on the inside generally makes one look nice on the outside.

Posted by: CD at May 30th, 2018 2:40 PM

Great piece! I could see this inspiring people to take future developments in anti-aging technology more seriously, and perhaps helping produce a cultural change that would improve the funding situation for SENS.
In the interest of helping, I must point out that there are several somewhat jarring tense discontinuities throughout the piece, which would make it more readable if corrected. For instance, you go back and forth between talking about being 85 as a (fictional) present, reminiscing about anti-aging treatments you have previously received, and talking about being 85 as a point that will occur in the future. Using one tense throughout would be better, in my opinion (I write for a living, sort of--I'm an academic philosopher).
Sorry for the unsolicited advice, but again, I really like what you've written here. Just offering suggestions that would make it slightly more readable.

Posted by: gheme at May 30th, 2018 2:49 PM

ill be 85 in 2072. if we dont have robust rejuvenation by then i will be very suprised

Posted by: scott emptage at May 30th, 2018 3:41 PM

@Cuberat

I have been on Keto for almost a year and I have dropped 50 lbs. During that time I went from 3 meals to 2 meals to 1 meal a day w/ intermittent fasting. All that without feeling hungry. I look better and feel better. I expect all of old fat people who want to live will make the transition to a better diet and get some exercise. I guarantee I will be signing up for life extension therapies as soon as they are available and I can afford them.

Posted by: Improbus at May 30th, 2018 3:46 PM

Great post Reason! As an interesting exercise, I've temporarily pasted the text on my site (I'll delete it soon), but used the more modern style of shorter paragraphs and shorter lines for improved readability and scanability (and changed the tense btw.)

What do people think, is this a more user-friendly style? Or does it appear too 'unscientific'?

Posted by: Justin at May 30th, 2018 5:10 PM

@Ariel, I make no such assumption. On the contrary, I expect that therapies developed with the skin and hair as the initial target will prove to be capable of repairing damage throughout the body, with some adaptation. But the skin is an easier initial target, and the obvious place to start.

"you cannot meaningfuly rejuvenate your appearance alone"
"You need to fix all 7 types of damage, only one of them -- cell therapy -- is very tissue specific"

I disagree. While all damage may be classified into 7 types, the exact nature of the damage may vary from one type of tissue to another. It would be nice if there was one magic bullet for each of the 7 types of damage, but variations in the way the damage accumulates in different tissues may mean we actually need seven families of treatments. Clearing senescent cells in the skin may require a different (though similar) treatment to that used to clear senescent cells in the liver or kidneys.

For example, you might find that each senolytic agent will work for several different tissue types, but not all, so you need a combination. The same might be true for crosslinking.

Posted by: Chris at May 30th, 2018 7:34 PM

Not sure,

You might be underestimating the ability of the FDA, Insurance Companies, and other entrenched industries & interests to block progress.

But I hope not, as I'll arrive at that age a decade before you.

Posted by: bmack500 at May 31st, 2018 8:11 AM

I reach 85 in the fall of 2025, so I have less time to reach LEV than most. However, I have some things going for me. I have studies my DNA genetics from 23andme and whole genome DNA analysis from Veritas Genetics, and found no troubling genetic factors in my genome. I have excellent health, blood pressure, HDL of 85, and many longevity genes, and gene SNP's and longevity alleles that I inherited. I have 6 Centenarians in my family tree, and feel I can make 110 on my existing genetics and lifestyle. I still run 2 miles a day, and get about 6 miles total steps/day counting walking. Since I feel I have about 30 years additional longevity over the typical person who dies at around 80 on average, I am probably in the same longevity bucket with the posters above who will reach 85 in 2055.

Posted by: Biotechy Marcks at May 31st, 2018 11:27 AM

@Chris, of course each tissue has specific issues but in general it is the same general approach. And that is uselles to use senolitics only for skin. Examples of parabiosis clearly show what goes on when you put young organ in the old inflammatory environment -- your organ will age much faster. In principle, you can make rejuvenation therapy only for skin but such an incomplete rejuvenation will vanish in a few years -- because chronic inflammation and other junk molecules will age your skin very quickly.

Posted by: Ariel at May 31st, 2018 11:48 AM

@ Biotechy Marcks: I found your post just as inspiring as Reason's original post. The fact you still run 2 miles a day is amazing. My Dad is a couple of yrs younger than you but couldn't run period (even if he does a lot of walking a couple of days a wk).

Posted by: Steven B at May 31st, 2018 2:55 PM

@ Biotechy Marcks: Good luck on reaching 110 since only one person in 3000 reaches 100! :) Are you planning on taking any anti-aging treatments in the next few years, e.g. senolytics etc? I'm 55 myself so I figure I'll wait for at least a few years and some positive trial results first.

Posted by: Justin at May 31st, 2018 4:56 PM

@Biotechy: I would sign up for cryonics, just in case.

Posted by: Antonio at May 31st, 2018 6:30 PM

@Biotechy Marcks: I am in the same boat as you, just a couple years older. I am on the similar strategy, wait a few years for positive results, and start taking some of the rejuv treatments. Hopefully, others besides senolytics will become available as we get closer to 70. In the mean time, just exercise, eat mostly right and hope for the best.

Posted by: Robert at May 31st, 2018 8:07 PM

@Robert, Justin: I agree with both of you in that one should proceed cautiously in trying and implementing new rejuvenation strategies that will inevitably soon start appearing in considerable numbers. You don't want to get too far in front of your skis, or your trip will end in disaster.

Posted by: Biotechy Marcks at June 2nd, 2018 6:13 AM

@Reason, perhaps consider putting this essay on the sidebar Required Reading right underneath The Million Year Lifespan. It's a classic similar to that one and inspiring.

Posted by: Morpheus at June 3rd, 2018 1:10 PM

Hi Reason,
When you are 85, I am sorry to say many of your friends will have already died.
The breakthoughs that you talk about will be overshadowed by the food industry and
Pharmacutical companies greed for money. Food is medicine, but the world has an
addiction to sugar/glucose which I feel is a major cause of many diseases today.
It is packaged in almost everything, even baby food! Look around you! Look at the rate of obesity in
our chidren today! Will they make it to 85? Pharmacutical companies do not want to lose
their guaranteed income from ill people. I wish it wasn't true, but this is reality. Some people like you (and me) will gravitate to companies promising longer life therapies, but sadly the majority wil not. Even if they did, how are you going to convince them to refuse the foods that are making them gain weight and aging faster? "You can't have your cake and live longer too".
And anti-aging breakthroughs? Look at intermittent Rapamycin, the proven success and the stigmatism. People could use it now but U.S. drug companies won't make and sell this senolytic because there's real no profit in it. Treatments take a lot of money, trials and time. Getting the U.S. government to recognize aging as a disease may help speed things up, and allow doctor's to prescribe anti-aging treatments. It's a battle against unseen forces at the top, holding back legislation.

Posted by: David G. Johnson at June 3rd, 2018 10:56 PM

@David G. Johnson rejuvenation therapies will be as big a buisiness as it is already therapies to adress aging will need reapplying over and over again which makes you a repeat customer

Posted by: scott emptage at June 4th, 2018 10:07 AM

@Reason, do you know (or anybody knows) if Bioviva has yet treatments in muscle gene therapy on the market? Thanks!

Posted by: Josep at June 4th, 2018 1:18 PM

@Josep: I believe they are close to it, but they are definitely working on mining the wealthy first. The prices I've seen touted are very high, much higher than most procedures obtained through medical tourism.

Posted by: Reason at June 4th, 2018 2:57 PM

@Josep, are you referring to Sarcopenia?

Good to know (if this is what Josep is talking about), Reason. My friend at the gym is very concerned about losing his muscles although I did tell him last year that they are working on treatments (cures?) for the loss. I have to assume it would be available inside of 10 years, at least outside the country for that timeframe.

Posted by: Robert at June 4th, 2018 5:53 PM

Thanks Reason and Robert!

Posted by: Josep at June 5th, 2018 2:43 AM

Scott, I will be a repeat customer of customer of antiaging therapies, however, I am not in the upper elite class where I can afford the expensiv therapies. And because of special interest groups that don't want to see people change their way of eating, and not taking prescriptions, that will fight these antiaging companies (by legislation and attack ads) in Washington and around the World, I do not see prices coming down, and I don't see therapies popping un your neighborhood.

Robert, be careful about muscle loss treatments. Companies still adverise "Growth Hormone treatments" on TV, etc. Gerovital comes to mind, but now they sell just plain "GH'. Well, GH does build muscle, and mnay body builders use it, but GH (Growth Hormone) is now known to stimulate the IGF1 gene that has to do with aging. (Google it!). Body Builders build muscle by taking GH and large amounts of protein but they don't live longer. Doctors started giving Gerovital to older people in convelescent homes to make them stronger. It worked but it shortens their life. A double edge sword.

Also it has been discovered that too much protein, like high meat, no veggies diets, or just taking a lot of protein shakes, also stimulates the IGF1 gene that increases aging.
It's best to eat more veggies and nuts (proein from them) and maybe a little meat if your a meat eater, but not much. Most centarians are not big muscled. You do need muscle for walking and lifting things but not to look like a muscle man to show off to other people.

Posted by: Snowbird at June 9th, 2018 9:09 PM

Biotechy and Steven B., at 90-next-July, I run 1½ miles a day except on Sundays and days when I swim ½ a mile. Most of this is done in pedal-to-the-metal sprint mode that leaves me gasping like a landed fish. I don't think I could do this if I hadn't kept athletically active as an adult, hadn't eaten from the rainbow, and hadn't taken supplements (including FOX04-dri, MitoQ, AMPK metabolic Activator, etc.) One pleasant surprise has been my rebuilding of lean muscle mass. I think maybe we might draw our octogenarian and nonagenarian stereotypes from the stooped and shuffling souls we see at shopping malls. I really think that those of us who are actively engaged in "longevinautics", given the interventions that have become available just this last year, are being prepped to live years longer than the historical norms for our ages. I'm wondering if we may not have already reached escape speed?

My hope is that the total body rejuvenation that David Sinclair has teased recently may arrive sooner rather than later. (He's asking, given full-body regeneration, how old would you want to be?)

I'm keeping my fingers crossed (:-))

Posted by: Bob Seitz at December 31st, 2018 10:58 PM
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