Scientists are working to eliminate senescent cells | Hacker News Reader

Scientists are working to eliminate senescent cells

theguardian.com

64 pointssambeau55 comments

While the article title is sensational, it’s encouraging to see SENS getting wider traction in the public imagination. A lot of the other proposed therapies seem to involve genetic engineering, and this one seems more somatic, more at the scale of designing a drug to work at the scale of cells, vs the scale of DNA. It seems, to my interested layperson’s mind, that a rough and ready treatment is more likely at this scale, albeit one less likely to result in 4-digit lifespans, measured in years. This does make one of my fears more imminent, which is what to do with things like teeth, the vitreous humor, extant arthritic damage, and other systems and organs, the effects of aging for which the body has more or less lost or never had cells in place that can be recruited for repair. Time will tell. With any luck, we’ll have loads of it!

> what to do with things like teeth, the vitreous humor, extant arthritic damage, and other systems and organs, the effects of aging for which the body has more or less lost or never had cells in place that can be recruited for repair

Sounds like we’ll have a healthy industry in healthcare and research for lifetimes to come.

> what to do with things like teeth,

False teeth have been available for quite a while now, not to mention implants.

> the vitreous humor,

Replace the eye with a camera? There are already people with experimental implants.

> extant arthritic damage,

Exo-skeleton? There are Japanese developments for construction workers that could probably be repurposed to help people be mobile.

> and other systems and organs,

Artificial hearts exist, dialysis works.

So yes, the health industry will be the biggest industry in the future.

I’m amazed that anyone thinks above normal individual longevity is a good idea. In my view it will be the end of human progress morally and scientifically rather than the beginning.

I'm amazed you can make such a sweeping statement with any confidence. What in your mind is "normal" human logevity? Because if by normal you mean "pre-industrial", then even discounting child mortality you're advocating for commplace plagues, famines and bad water affecting the number. We've been changing our environment, our bodies, and surpassing natural barriers since before we were sentient. Why should we stop now that we're just starting to get good at it?

Normal or natural human longevity is ~30-35 years. You can determine that because it is essentially a function of (average) body weight. The bigger your (species) is, the longer you live.

Really interesting book on the subject:

https://www.amazon.com/Sex-Origins-Death-William-Clark/dp/01...

TLDR: 2 unchangeable sexes + death (both of those) has proven to be the most effective reproductive strategy, beating out every competitor by a huge margin. This means there is a very good reason for death to exist and death is a "new" thing. There was a very long time when animals (well ... technically multicellular bacteria colonies) just didn't ever die. Some of those are alive right now and are hundreds of thousands of years old, at least. We know about the effectiveness because there are species (none are animals) that are still alive that predate evolution's "invention" of death, that have competed to conquer the earth, and they failed dismally. And we know about the 2 unchangeable sexes because there's a lot of variation in sexes, none very successful (there even are asexual animals, and animals that can change their sex, and animals with different sex arrangements. Some have small differences (like males giving birth), and some are hugely different, like true asexual animals)

> the most effective reproductive strategy

What does this have to do with anything?

We left that equilibrium point when we developed systematic agriculture.

> This means there is a very good reason for death to exist

No it doesn't. It is simply necessary for genes to compete.

We are not our genes.

> We are not our genes.

Indeed, it's much worse than that. We are just a tool to help in survival of those genes. We are one tool among many for those genes and not nearly as important everybody seems to think we are.

Why do you believe it will signal an end?

Because life is given meaning and focus by its brevity. Because generations give us the constant possibility of change and new ideas.

Perhaps a person's psyche will change, given the change in perspective a longer life could induce. After all, a child has many erroneous perspectives, and yet is able to adapt. With longer, healthier lives may come the freedom to re-examine old ideas. I hesitate to make sweeping statements, however, since this is psychology.

What I can say is that it is fallacy to assume one can extrapolate into the unknown by projecting linearly, or even statically, the known. In this case, why should the old be locked into old views? Wisdom urges always incorporating the latest information. People persist in wrong thinking after being shown right - this ego grasping may be a symptom of short lives, for some. And yet, certainly the desire to live longer is, at (the very) least in part, ego grasping, but that does not mean a sentience with infinite longevity will engage in ego grasping forever. Forever is a long time. -Eventually even the most ego wrapped ``child'' should grow out of it, if he or she grows at all.

New challenges give us the possibility of change and new ideas. Certainly re-doing life's challenges again with new minds does induce humanity to take on new ideas, as you say. Maybe there is something of the breadth first vs depth first search style in this comparison. Surely both can have their place.

What is presented without evidence can be dismissed without evidence. But this statement can be dismissed twice: Not only is it not established that brevity gives life meaning, it isn’t established that life even has or needs meaning!

People form rigid organizational structures around themselves. At first these structures advance progress, but eventually they run their course and become a burden. Natural death of the key members of the organization is one way to promote progress within. Absent that we're looking at massive stagnation.

The death of the organization itself is another way, which is basically the foundation of the free-market capitalism.

That's an awfully narrow view. Even today we see 80 year olds learning all sorts of new paradigms. Granted they're sadly the exception rather than the rule, but that's a cultural issue we can fix.

The biggest cause of the stagnation you mention IMO is people thinking they deserve something simply because they've physically existed for longer. With the advent of the information age that illusion is becoming harder to maintain. Might take a few generations to develop the correct institutions, but longer lived humans could readily adapt. And that's assuming humans stay otherwise the same physically. Any knowledge that could lead to 4 digit lifetimes will almost certainly come with enough knowledge to turn us into legit cyborgs, or genetically engineered superhumans if we want, and all bets are off at that point.

> Even today we see 80 year olds learning all sorts of new paradigms.

I said nothing about old people's ability to contribute, rather I was speaking about organizations staffed with the same people for a long time.

See also: "Science advances one funeral at a time." http://www.nber.org/digest/mar16/w21788.html

It will be solved by a brain-rejuvenating drug. Same people, but fresh brains. And some of those brains will be rejuvenated so much that they will leave the organizations anyway, to pick up music, or maths :).

Problem is you accumulate status and groupthink within an organization. Rejuvenating brain doesn't help against that, unless you plan to wipe it altogether.

A property of a young brain is that of starting afresh, being able to change and follow entirely new paths. So yes, I suppose that a rejuvenated brain would end up partially wiping itself. On the other end, what's the fun of living forever if you always have to be the same person?

As am I. Science advancing one funeral at a time is an institutional and cultural failing, not a natural law.

Our systems of governance alao used to advance one funeral at a time as well, we eventually figured out many ways around that.

That is indeed a potential problem. But I think “let everyone alive now and forevermore die” is a poor solution.

I didn't offer that solution.

I don't want to die. When I hear statements like yours, what it sounds like to me is that you want me to die. I find that morally reprehensible. No one should have to die until they want to; that's the ultimate justice. If you don't want to live after 100, or 75, or 35, call it what it is. There is no moral high ground in telling other people to commit suicide.

Do you believe in inserting a heart stent to save someones life from coronary heart disease, potentially buying them many increased years.

Longevity science is basically all of human healthcare practices, but iterated ad infinitum. Where do you draw the line?

We only lived to our 30s just a few hundred years ago. Was that the natural way things should be?

The poster I responded to was mooting 4 digit length lifespans. This isn’t about living a longish life. Maybe super normal would have been a clearer term.

> We only lived to our 30s just a few hundred years ago.

That's not true. Life expectancy used to be strongly bimodal, with a lot of people dying as children, and the rest living out a more or less modern lifespan (unless they caught some disease). Sure, average life expectancy at birth was around 30, but average life expectancy at age 18 was way higher.

Say no to heart stents, btw. Do the research.

... you arrogantly said to a medical professional working at a hospital ...

Sorry if I came off as arrogant. I want more people to know about the uselessness of stents.

https://www.nytimes.com/2018/02/12/upshot/heart-stents-are-u...

You don't have to take the drugs if you don't want to and can happily die at ~85

Alternatively you can take the drugs and die surprised at ~85.

Honestly, I just don't want to die. We can work out the rest once we get there.

You can keep your normal lufespan, thank you very much, I would personally go for double.

>the effects of aging for which the body has more or less lost or never had cells in place that can be recruited for repair.

So give it cells to be recruiter for repair! Stem cells seem promising for these things.

It is a huge bummer to use a platform fundamentally designed to fail though. All of this has to be a stopgap until we have digital consciousnesses, I hope.

Yeah we just need to learn to program large scale DNA to be compatible with our own DNA code ... which we can't even read in a meaningful way ... I mean we can get the binary code, but we don't understand even a basic "if" instruction. Yeah, I'm going to go out on a limb here and say it's not going to happen tomorrow. This'll take 100+ years even at our accelerating pace of development.

(teeth being an exception though)

As documented by Dr. Rhonda Patrick (and others), fasting can trigger cellular autophagy and reduce senescent cells without the use of drugs. https://www.foundmyfitness.com/news/t/fasting

Well. To be fair these theories are based on studies using mice. Is there some parallel to humans? Likely. But that nonetheless remains to be seen.

Sadly it takes a century to do those studies

There’s a substantial tradition of fasting in Christian (especially Orthodox) and Islamic faiths. I’d say that even if we don’t know the mechanism of action, the fact that it was something preserved through the years rather than abandoned means it merits thought about its benefit.

Oh we definitely know the mechanisms of action, especially for short term metabolic benefits. For lifespan studies though, the data just isn't there.

I don’t think religious fasting is practiced to grant one a longer lifespan.

Religious fasting won't induce autophagy. At least in those religious fasting traditions that I know of (Christian lent and Islamic Ramadan) observers can consume calories each day. Autophagy (IIRC) only starts after several days with zero caloric intake.

Valter Longo has conducted human studies pointing to the veracity of this effect, at least with MS patients. Certainly early days yet, but compelling nonetheless. https://www.sciencedaily.com/releases/2016/05/160526151941.h...

Does intermittent fasting count as real fasting?

I believe she suggested a 72 hour fast once every three months or so. I also read the abstract of a study that claims fasting for 24 hours increases the concentration of some chemical that clears sways senescent cells. (But I can’t find it now, sorry)

I think senescence may be largely driven by viral infections. The top gene associated with senescence is hijacked by many viruses to lock the cell cycle into a specific point and optimize energy production, which viruses need to propagate.

https://medium.com/@InfinoMe/senescence-links-between-heart-...

We need better antivirals so we can kill off stuff like Epstein-Barr that infects so many of us for a lifetime.

This is curious:

[...] says Kirkland, who is also running a handful of clinical trials at Mayo for repurposed cancer drugs and natural products that have been shown to kill senescent cells in mice. [...]

What are those "natural products" I wonder?

Natural product is just a pharma industry term referring to a very large category of drugs derived from natural sources https://en.wikipedia.org/wiki/Natural_product. Not related to naturopathy or other nonsense.

https://www.clinicaltrials.gov/ct2/show/study/NCT03430037

https://www.clinicaltrials.gov/ct2/show/study/NCT03675724

> In a lab just south of San Francisco...

I’m always so amazing that Silicone Valley is so obsessed with finding the fountain of youth, yet so willing to dash their own youth upon the rocks by working long hours, putting off having kids and starting a family, etc.

One person's dashed youth is another person's life well spent

I think we are the bubble generation, like the poor schmuck who died last in the ww2, humans will live forever and conquer the space.

But that means we'll be the youngest, hottest, and coolest people in the afterlife.

damn, good point.

Do you want to be the hippest dead person or the lamest, out-of-touch alive person? Hard decision

Live fast, die young and be a good looking corps

Well, I messed that up already. Too late to fix it.

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