An anti-aging strategy that works in mice is about to be tested in humans | Hacker News Reader

An anti-aging strategy that works in mice is about to be tested in humans

scientificamerican.com

221 pointsmolecule64 comments

There are quite a few comments skeptical about whether this would actually prolong life, but that result is not the only possible benefit. Even keeping our same lifespan, but not picking up age-related diseases, aches and pains, and blindness would be a huge benefit to older folk. (And I mean those of us in our 40s and 50s, who already curtail activities due to aging, not just people over 80.)

Seriously, having been though some health problems, and seeing how much your quality of life can suffer, I think some people would willingly take a slightly shorter lifespan for increased quality of life as we age.

Are these drugs the answer? I have no clue. But the direction of the research is encouraging, no matter how long we all live.

Health span over life span

In general in biology there is a simple criteria about the interest of an article:

- If it is tested in vitro, not only those results do not translate to human health issues (it is not in a living tissue which is a complex milieu, not simply the juxtaposition of cells), but commercial cell lines are not representative of normal cells, as they reproduce indefinitively.

- If it is tested on a mammalian animal model, it better but obviously mammalian species are different from each other at the organe level (for example the tail is used for thermoregulation in mouses).

- The best thing for evaluating any human impact, is a phase III of a clinical study.

This is largely a promo for Unity Biotechnology and the associated labs. It fails to mention, e.g. SIWA Therapeutics and their work on antibodies, Oisin Biotechnologies and their gene therapy DNA constructs for destroying cells based on internal chemistry, the company that David Sinclair is starting for senolytics, that Betterhumans has beaten Unity to the punch and is currently running phase 0 human pilots of dasatinib and quercetin on a non-profit basis. Also that senescent cell clearance didn't magically spring into being in 2011, but appears clearly in Aubrey de Grey's position paper on human rejuvenation in 2002, and the Methuselah Foundation, SENS Research Foundation, and others have been advocating hard for more work in this direction in the face of a research community that rejected it for a decade.

But hey, if you beat the competitors to be the first to raise 9-figure sums of venture capital, then you too can engineer attention to shine on you only, and rewrite history more or less as you like for a while.

So far all ways to address aging in mice have slowed aging by tinkering with metabolism, but slowing down the damage accumulation. They all produce much larger effects in short-lived species, probably because long-lived species have evolved to have many of these metabolic items turned on already. Calorie restriction extends life by 40% in mice, and I can assure you that while it is pretty beneficial in humans, you are not going to add more than a couple of extra years. Senescent cell clearance is the first way to address aging that involves repair of damage rather than slowing it down: we have no idea how the size of benefit in mice will translate to humans. So 25% gains in mice can be exciting here, whereas for any slowing-aging-only approach it would be a yawn.

Isn't this yet another case for keto/intermittent fasting? It is well known that in a fasting state you trigger cell autophagy -> essentially force healthy cells to eat dead or diseased cells for energy...

And btw...fasting is free, safe when done properly, and something anyone can do today

I would much rather fast than ingest a drug pushed by big pharma...even if it did work and triggered the same response

The longevity benefits of fasting/caloric-restriction also appear to work through the clearing of some cells ('autophagy'); see for example:

https://en.wikipedia.org/wiki/Autophagy#Caloric_restriction

<Conjecture> if you were a hungry body, which cells would you cannibalize first, healthy cells or old malfunctioning troublemakers?

You just made a mind boggling amount of assumptions in one sentence.

Fasting is also an effective remedy for a boggled mind.

Took me a while to find, but this method apparently only increases the life span of mice by 25%. Given how mice are prey animals - i.e. they aren't meant to live long - I don't anticipate the same results with Humans. Although, it may help reduce risks of diseases.

It'll be interesting to see results.

I'll take an "only" 20 year life span increase.

"I plan to live forever, of course, but barring that I'd settle for a couple thousand years. Even five hundred would be pretty nice."

— CEO Nwabudike Morgan, Alpha Centauri

Hell I'd take the normal span with my health and my mind intact. I've seen old brains. It scares me.

Yeah, I wonder if senolytics have a positive effect on the brain.

We already have a potential treatment for age-related cognitive decline: vampirism (kinda). https://www.scientificamerican.com/article/fountain-of-youth...

Their point is that the lifespan increase is probably unique to mice. Mice are designed to die quickly.

So are we. You think 80 some odd years is a long time?

Most animals die sooner.

80 years is too short. That's only 20 American presidential terms.

I'll take a 20 year lifespan increase at least every 20 years. Preferably a 20 year lifespan increase every 5-15, for a healthy safety margin.

Even if there is 0% increase in median lifespan, they describe many effects which would make aging a much less miserable and debilitating experience. That alone is a win. Take this bit:

"can restore lustrous hair and physical fitness to ageing mice"

Think of it! Finally, a cure for baldness! And, yeah, less of a decline in fitness would be nice, too.

it just means bald with shiny hair.

Organs improved too

It does provide an interesting model why ~80 is considered an average lifespan, but some people can live up to ~120 and be unusually heathy at 80/90 etc.

I thought a huge part of the problem is mice are not that similar to humans (lots of things have different effects on mice versus humans) but mice are really easy/cheap to test with compared to larger mammals that are a bit closer to humans. We could be missing a lot by not testing stuff in humans that has zero/deleterious effect in mice.

Some papers showing direct connections between senescent cells and specific aspects of aging, in many cases turning back that aspect by removing the senescent cells.

Osteoporosis: https://doi.org/10.1038/nm.4385

Fatty liver disease: https://doi.org/10.1038/ncomms15691

Disruption of platelet formation: https://doi.org/10.3389/fonc.2017.00188

Osteoarthritis: https://dx.doi.org/10.1038/nm.4324

Disruption of regeneration: https://doi.org/10.3389/fcell.2017.00049

Lung fibrosis: https://doi.org/10.1183/13993003.02367-2016

Pulmonary function in general, including tissue elasticity: https://doi.org/10.1172/jci.insight.87732

Atherosclerosis: http://dx.doi.org/10.1126/science.aaf6659

Vascular calcification: http://dx.doi.org/10.18632/aging.101191

Chronic kidney disease: https://doi.org/10.18632/oncotarget.17327

Cardiac hypertrophy: https://doi.org/10.1371/journal.pone.0182668

Cardiac fibrosis and function in general: https://doi.org/10.1093/eurheartj/ehx454

I would be surprised if people weren't already testing this, e.g. in China where there is less regulation.

I think that could be a trend: US/European researcher publishes hypothesis, and Asian researcher secretly tests it on humans, and if it works, publishes it and/or becomes first to market.

What do you think the solution would be, should this take off? Wrapping early stage trials in a veil of secrecy?

I'd say we should encourage this, but just make sure our intellectual property agreements are strong enough so that both parties benefit from their contribution.

In my view, we need to be moving much faster on developing technologies, drugs, and therapies. If some societies are able to help out, we should be grateful and welcome that - so long as the subjects all consent.

So basically you would applaud weaker ethical rules in China?

There is no doubt that China has weaker ethical rules compared to the West, but I think in this case, as long as the person consents, what's the problem?

Do you necessarily think that it's more ethical to have laws or rules that forbids suicides or self-harm regardless of what a person wants?

Making a choice to protect people trying new treatments keeps those people safer but the trade-off is that you develop new treatments slower, which means more people suffer and die waiting for treatments.

Developing quickly versus safely are different decisions, but I don't think one is purely stronger or weaker than the other.

I wonder if exercising contributes to killing off these senescent cells. In muscle building one is breaking down and rebuilding muscle cells, this might as well prevent cell "aging" and going into senescence.

Maybe exercising increases activity in the inmune system which contributes to killing more senescent cells?

"I wonder if exercising contributes to killing off these senescent cells. In muscle building one is breaking down and rebuilding muscle cells, this might as well prevent cell "aging" and going into senescence."

I think this is already known and understood - at least with muscle and bone cells. My understanding was that by putting energy production stresses on your cells, you weed out the ones that perform poorly. Specifically, you weed out those cells whose mitochondria are less efficient at producing energy.[1]

So there is a selection process that takes place, over time, in your own cell population.

I find this very interesting but I have also grown very pessimistic about its import ... people that don't like exercising will do anything not to exercise so it really doesn't matter.

We don't need any new findings that demonstrate the (clear, obvious, nearly immediate) benefits of exercise. What we need are fewer cars and more walking.

[1] I highly recommend Nick Lanes first two books - _Oxygen_ and _Power, Sex, Suicide: Mitochondria and the Meaning of Life_.

Just thinking about the societal implications of this. For example, death is one of the few things that causes turnover in the Senate.

It seems ironic that the mechanism here (killing off old cells) enables humans to live longer, thereby possibly enabling these same humans to case society to age.

Life extension will be horribly dystopian unless we can also find ways to restore neuroplasticity and enable re-learning-- a kind of "second childhood." Otherwise it'll be a bunch of immortal old curmudgeons sitting on top of society saying "get off my lawn!"

Personally I'm not sure I'd even want too much life extension without neuroplasticity restoration and quality of life extension. I'd rather be dead than walking dead.

I'll take immortality and term limits, please.

Not going to prevent aging as well as people think.

As cells age, the risk for mutations occuring when they divide increases. The reason these cells stop dividing and become senescent is because dividing elderly cells poses a high cancer risk.

I think this may buy the trappings of youth (plump skin, clear eyes, etc) at the cost of a higher risk of cancer.

Yes, but the remaining non-senescent cells are obviously not damaged too much, and thus CAN divide - perhaps they did not divide as often in their lifetime, their ancestors were not as stressed, or their DNA was not compromised. If you make room for those cells to divide, that should be a good thing.

gametes never really stop dividing...

Where do I sign up? (-:

Where's the catch?

7 Billion humans

The universe is big. There is energy everywhere.

Meanwhile, the Earth is not, and we still primarily use fossil fuels.

But maybe someday we'll have terraformed Venus and Mars, and found a way to travel those light years. Probably not this century, though.

Long-term survival could be the sort of problem that requires people to think about it for 100-500 years beyond kindergarten. Moreover, societies here on Earth could benefit from people caring more about the impact they will have beyond their (currently) inevitable death in 0-100 years.

It could actually be beneficial to the planet. If today's politicians knew that climate changes, social inequalities and water shortages would actually affect them in their lifetime, they might reconsider the short term benefits of accepting donations from harmful lobbyists.

In other words, it could redefine "short term".

All our current research rates might be dramatically improved if our best scientists don't die all the time.

Conversely, "A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it." -- Max Planck

(Usually paraphrased as "Science advances one funeral at a time.")

This is an over used crutch. Any truth in it comes mostly from a tendency to fund senior researchers over junior ones.

The earth was big. There is oil everywhere.

Unless we can come up with some sweet carbon sequestration tech, that's actually a liability.

I guess the trick is to mix bamboo with cacti and a gene to produce longterm anti-fungals and seed the deserts.

Source? That sounds pretty neat.

The catch is that it will take a lot of time until this kind of study gives definitive results. People already live quite long, so longevity studies are usually multi-generational.

It could take a lot of time if we wait for the definitive results, but probably Big Pharma will find a way to sell it to us before that happens.

Summary: Kill cells that have stopped dividing, but that are still alive. (Called: Senescent cells.)

Don't prevent them from entering this state (which could cause tumors), just kill them if they do enter this state.

Hard part: Each organ/tissue has different types of cells, so each needs a unique medication to kill those cells.

are you an auto-summary bot?

thankyou for the downvotes, it was a genuine question. I see a lot of this bot-like behaviour on HN these days

A cursory review of their comment history would lead me to think that they're not.

Huh, etymology is a lot of fun.

https://en.wikipedia.org/wiki/Seneschal

Elderly stewards are always pulling shit; it's a trope.

Reply on news.ycombinator.com