Three New Longevity Startups(leafscience.org)
leafscience.org
Three New Longevity Startups
https://www.leafscience.org/three-groundbreaking-longevity-startups/
63 comments
What is your opinion of using a monoclonal antibody against 7KC instead of cyclodextrin since mAbs are very well understood from a regulatory and PK/PD point of view. In your review I only see that you discuss 7KC antibodies as a method of screening for people who could benefit from your therapeutic idea.
Great question. Two problems with making a therapeutic antibody against seven KC. One is that we are not sure how good the seven KC antibodies are yet. We are working on this. The problem there is that 7KC only differs from cholesterol by one atom. The other problem is that the 7KC that we are worried about is inside of cells, so our drug is designed to mechanically pull the seven KC out, which antibodies can't really do. Also, cyclodextrins are very well accepted by regulators, it's just that they are usually used as excipients rather than as Active Pharmaceutical Ingredients (APIs). There are two examples of cyclodextrin APIs already, however, one approved and one in late stage clinical trials.
Cool, thanks for the reply. Are the approved use parenteral? Have you considered aptamers?
Yes, we are looking at IV, as others have done already clinically. We aren't looking at aptamers or other clever ways of binding small toxic biomolecules. I hope that other groups are!
This is a pretty interesting paper: https://stm.sciencemag.org/content/8/333/333ra50
Is there a chance that you are developing CD that target 7KC but at the end of the day, it dissolved chol-containing plaques inherently and that's where you'll derive the benefit from?
Is there a chance that you are developing CD that target 7KC but at the end of the day, it dissolved chol-containing plaques inherently and that's where you'll derive the benefit from?
More on Underdog Pharma: https://www.fightaging.org/archives/2019/11/an-interview-wit...
"We've taken a well-known and extremely safe compound, and have created novel derivatives that can specifically target the toxic biomolecule that drives the development of atherosclerosis, the cause of most heart attacks and strokes."
I'm excited for this one. Seems like a reasonable possibility for success addressing a huge killer.
"We've taken a well-known and extremely safe compound, and have created novel derivatives that can specifically target the toxic biomolecule that drives the development of atherosclerosis, the cause of most heart attacks and strokes."
I'm excited for this one. Seems like a reasonable possibility for success addressing a huge killer.
> The company is focused on a class of molecule known cyclodextrins, and have candidates capable of efficiently binding and sequestering 7-ketocholesterol. This form of oxidized cholesterol is of great importance to the progression of atherosclerosis, and possibly other age-related conditions as well.
The thing is cyclodextrins have been linked to causing deafness, in as little as a week. As per https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676048/ and https://www.wsj.com/amp/articles/deaf-or-death-in-drug-trial...
Heart disease or hearing – tough trade-offs. Here’s to hoping that they’ve engineered a novel compound without any of the downsides.
The thing is cyclodextrins have been linked to causing deafness, in as little as a week. As per https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676048/ and https://www.wsj.com/amp/articles/deaf-or-death-in-drug-trial...
Heart disease or hearing – tough trade-offs. Here’s to hoping that they’ve engineered a novel compound without any of the downsides.
Are they engineering the macrophages to produce the enzyme? How does it work?
I think longevity is vastly underestimated. Besides the natural innate desire to live longer, every extra year of healthspan is an opportunity to reap benefits on long term investment in friends, family and financial instruments. Knowing that you may live to 150 changes how you might approach investing and spending your time in money and skills development. People with the conscientiousness and forethought to apply themselves to important but not urgent tasks might experience compound interest the likes of which we have never seen before. Imagine if Warren Buffet was only half way through his healthspan.
> I think longevity is vastly underestimated.
Many people would give up their entire life fortune, any inheritance to their children, just to live for a few more years. People have been killing and dying searching for the fountain of youth for centuries.
Everyone is going to die eventually, yet the extremes people go to extend life is unlike any normal supply and demand curve.
I'm not sure there's anything more overestimated and over-hyped than longevity.
Many people would give up their entire life fortune, any inheritance to their children, just to live for a few more years. People have been killing and dying searching for the fountain of youth for centuries.
Everyone is going to die eventually, yet the extremes people go to extend life is unlike any normal supply and demand curve.
I'm not sure there's anything more overestimated and over-hyped than longevity.
There is not enough funding or investment in longevity to consider it over-hyped. Compare it to, say, AI and VR. Or even meat substitutes.
> There is not enough funding or investment in longevity to consider it over-hyped. Compare it to, say, AI and VR. Or even meat substitutes.
You're very much mistaken.
The National Institute of Health gets $31B of government funds every year for research. The NSF gets $8B, NASA gets $20B, and DARPA gets around $3B. So healthcare research gets roughly 50% of the entire U.S. public research budget, and that's not including private investment.
It's difficult to pull accurate numbers, but meat substitutes, VR, and even super-hot AI get far less every year, it's nowhere near healthcare research.
Extending life has been a priority of the US government for many years, largely because it's politically popular. Everyone rich or poor wants to live longer.
You're very much mistaken.
The National Institute of Health gets $31B of government funds every year for research. The NSF gets $8B, NASA gets $20B, and DARPA gets around $3B. So healthcare research gets roughly 50% of the entire U.S. public research budget, and that's not including private investment.
It's difficult to pull accurate numbers, but meat substitutes, VR, and even super-hot AI get far less every year, it's nowhere near healthcare research.
Extending life has been a priority of the US government for many years, largely because it's politically popular. Everyone rich or poor wants to live longer.
That is "traditonal" healthcare, where the target age is 70-80ish, with basically no means to get past that.
This is very different from what longevity research (like in the article) is tackling, and almost non of that money (public or private) is invested there.
This is very different from what longevity research (like in the article) is tackling, and almost non of that money (public or private) is invested there.
> That is "traditonal" healthcare, where the target age is 70-80ish, with basically no means to get past that. This is very different from what longevity research (like in the article) is tackling...
If you're searching for a cure for cancer, heart failure, or any of fatal health ailment, you are by definition trying to extend people's lives. The entire purpose of healthcare is to extend both the length and quality of people's lives.
If you're searching for a cure for cancer, heart failure, or any of fatal health ailment, you are by definition trying to extend people's lives. The entire purpose of healthcare is to extend both the length and quality of people's lives.
A few people, mostly in fairy tails, maybe.
Many people, however, won't even do something simple and enjoyably like frequent moderate exercise to improve their longevity.
Many people, however, won't even do something simple and enjoyably like frequent moderate exercise to improve their longevity.
That's being ungenerous, most people that don't exercise don't perceive it as something enjoyable. Imagining people that behave differently than you as idiotic is both unkind, and strategically foolish, as it will lead you to underestimate your enemies.
Check your presumptions and maybe consider taking your own advice. I'm among the people who don't, and I don't think that I'm idiotic. (but maybe I'm mistaken on that point, because after rereading my post several times I still can't figure out how I inspired this response from you)
The poster I was responding to claimed "yet the extremes people go to extend life is unlike any normal supply and demand curve. I'm not sure there's anything more overestimated and over-hyped than longevity." -- and I think the is transparently untrue because a great many people do not act as though it is incredibly important to them.
The poster I was responding to claimed "yet the extremes people go to extend life is unlike any normal supply and demand curve. I'm not sure there's anything more overestimated and over-hyped than longevity." -- and I think the is transparently untrue because a great many people do not act as though it is incredibly important to them.
Reading this article makes me very glad that I've been donating to SENS for some time now. They are doing awesome work:
https://www.sens.org/get-involved/donate/
https://www.sens.org/get-involved/donate/
I learned a lot through this, thank you for sharing.
I run a sperm freezing company (YC S19) incubated at Harvard and we've always thought about freezing sperm as an extremely logical pairing with any life extension technology; sperm can be frozen indefinitely with no loss in quality (as far as we know), you could have 30-year old sperm frozen for us when you're 130.
Since sperm develops mutations over time (~1 every 8 months) and DNA fragmentation is associated with all manner of congenital conditions like autism, younger sperm is generally speaking healthier.
Just wanted to share since it's something we talk about internally quite a bit. What does it mean to live forever if you lose all your family members along the way? How will society change to accommodate?
I run a sperm freezing company (YC S19) incubated at Harvard and we've always thought about freezing sperm as an extremely logical pairing with any life extension technology; sperm can be frozen indefinitely with no loss in quality (as far as we know), you could have 30-year old sperm frozen for us when you're 130.
Since sperm develops mutations over time (~1 every 8 months) and DNA fragmentation is associated with all manner of congenital conditions like autism, younger sperm is generally speaking healthier.
Just wanted to share since it's something we talk about internally quite a bit. What does it mean to live forever if you lose all your family members along the way? How will society change to accommodate?
Longevity is a interesting one because there are so many studies out there that have looked into calorie restriction as having a large positive influence on healthy aging...
At what age would these treatments be applied? How often?
this is mostly research. there are a lot of things you can do to slow down aging right now - almost orthogonal to your age: sleep 7+ hours per night, hit the gym (mix of cardio+strength), eat high quality food - the less processed the better - also try to eat a plant based diet, reduce the level of stress in your life, properly hydrate yourself, hang out with people you like, get a pet, get a side project that is a work of love, learn something every day, read books, reduce your social media (and media in general) consumption.
> eat a plant based diet
I agree with everything else you've said, but the jury is definitely out on this one.
I agree with everything else you've said, but the jury is definitely out on this one.
The current life expectancy for Iceland in 2020 is 83.07 years, a 0.18% increase from 2019. [1]
Life expectancy for Hong Kong is 84.7 years. [2]
Based on a comparison of 158 countries in 2013, Maldives ranked the highest in fish consumption per capita with 166 kg followed by Iceland and Hong Kong [3]
Hong Kong also beats most countries in beef consumption, out-eating Americans by nearly 50% per capita. [4]
So of the countries in the top 10 for life expectancy, we see a lot of meat in the diet. India has the most vegetarians of any country (at 38%). And their life expectancy ranks 133rd at 69.4 years.
[1] https://www.macrotrends.net/countries/ISL/iceland/life-expec... [2] https://en.wikipedia.org/wiki/List_of_countries_by_life_expe... [3] https://www.helgilibrary.com/indicators/fish-consumption-per... [4] https://beef2live.com/story-world-beef-consumption-per-capit...
Life expectancy for Hong Kong is 84.7 years. [2]
Based on a comparison of 158 countries in 2013, Maldives ranked the highest in fish consumption per capita with 166 kg followed by Iceland and Hong Kong [3]
Hong Kong also beats most countries in beef consumption, out-eating Americans by nearly 50% per capita. [4]
So of the countries in the top 10 for life expectancy, we see a lot of meat in the diet. India has the most vegetarians of any country (at 38%). And their life expectancy ranks 133rd at 69.4 years.
[1] https://www.macrotrends.net/countries/ISL/iceland/life-expec... [2] https://en.wikipedia.org/wiki/List_of_countries_by_life_expe... [3] https://www.helgilibrary.com/indicators/fish-consumption-per... [4] https://beef2live.com/story-world-beef-consumption-per-capit...
These are highly confounding statistics. Meat consumption grows with wealth and lifespan also grows with wealth. To say lifespan grows with wealth because of meat consumption doesn’t make sense.
Hong Kong’s beef consumption doubled since 2003. I’d wager your average elderly American ate more meat in their life than your average Hong Kong resident.
Source: https://medium.com/@ecyY/meat-consumption-growth-in-hong-kon...
Hong Kong’s beef consumption doubled since 2003. I’d wager your average elderly American ate more meat in their life than your average Hong Kong resident.
Source: https://medium.com/@ecyY/meat-consumption-growth-in-hong-kon...
Their life expectancy keeps increasing right along with their meat consumption:
https://www.macrotrends.net/countries/HKG/hong-kong/life-exp...
https://www.macrotrends.net/countries/HKG/hong-kong/life-exp...
More like their wealth.
If you look at the article I linked to, it shows relatively flat beef consumption until the mid 2000s.
I’m not saying beef will kill you, but picking two or three rich countries that eat a lot of meat — and have a huge amount going for them in other ways — and comparing them to India is not science or a statistically significant thing. It’s like comparing teacher salaries and alcohol prices in the 1970s and saying one causes the other when they’re both the result of inflation.
If you look at the article I linked to, it shows relatively flat beef consumption until the mid 2000s.
I’m not saying beef will kill you, but picking two or three rich countries that eat a lot of meat — and have a huge amount going for them in other ways — and comparing them to India is not science or a statistically significant thing. It’s like comparing teacher salaries and alcohol prices in the 1970s and saying one causes the other when they’re both the result of inflation.
No it shows a rising trend in meat eating beginning in 1961. Hong Kong has been prosperous for generations, by the way. It's not a recent phenomenon that Hong Kong has gotten wealthy.
You can look at the entire top 10 list of countries by life expectancy. They have plenty of meat consumption. There are no clinical studies implicating meat in shortened lifespans.
But people blindly spout off that a plant based diet is supposedly healthiest for you. There's no evidence to support that.
You can look at the entire top 10 list of countries by life expectancy. They have plenty of meat consumption. There are no clinical studies implicating meat in shortened lifespans.
But people blindly spout off that a plant based diet is supposedly healthiest for you. There's no evidence to support that.
So has almost every other statistic... if you singled out every other factor such as internet access, technological advancements, health care, medicine and just gave people meat as a substitute for all of that do you think that would suddenly increase their life expectancy by 50%?
Some big confounding factors there. Hong Kong and Iceland are also very wealthy compared to India.
There is a fortunate coincidence here. There are wealthy vegetarian castes in India, and India tracks demographics by caste, so it's likely that the data is out there for us to figure this part out.
An alternative is to do something like follow second-generation Western people of Indian origin. I know at least one study of Tuberculosis in the UK tested the effect of vegetarianism there and used the British Asian sub-population to do so, so there's probably some info there too.
I don't know of any other large vegetarian groups.
An alternative is to do something like follow second-generation Western people of Indian origin. I know at least one study of Tuberculosis in the UK tested the effect of vegetarianism there and used the British Asian sub-population to do so, so there's probably some info there too.
I don't know of any other large vegetarian groups.
Well at 133rd there are plenty of 3rd world countries above them. There's only 185 countries on the planet. It certainly shows that meat consumption doesn't hurt.
[deleted]
From the OP
> AGEs can also be encountered in foods, particularly foods that have been exposed to high temperatures, such as in grilling or frying.
I wonder if non plant based diets promote more grilling and frying hence the bad wrap.
> AGEs can also be encountered in foods, particularly foods that have been exposed to high temperatures, such as in grilling or frying.
I wonder if non plant based diets promote more grilling and frying hence the bad wrap.
there is some research out there that suggests you may live longer if you can actually pull this off.
Can you give a pointer to the research on non-social media consumption decreasing longevity?
From what I read physical fitness correlates much better with it than mental fitness.
From what I read physical fitness correlates much better with it than mental fitness.
Wild guess but this could be related to stress. Specifically, the closer you can get to stoic and indifferent to the 'successes' of other people, the more content you are likely to be.
Without the corrosive influence of social media, you might also be more likely to live a more authentic life that you find personally meaningful.
That said, I doubt everyone has the same relationship with social media that I had. I found myself influenced by it even in small doses, and it always felt like it was detracting from my wellbeing. Going cold turkey ended up being a life-changing decision for me and I wouldn't dream of going back.
Without the corrosive influence of social media, you might also be more likely to live a more authentic life that you find personally meaningful.
That said, I doubt everyone has the same relationship with social media that I had. I found myself influenced by it even in small doses, and it always felt like it was detracting from my wellbeing. Going cold turkey ended up being a life-changing decision for me and I wouldn't dream of going back.
being social and interacting with people is actually beneficial. increasing your stress level by watching mainstream media and consuming regurgitated content probably is not.
Complete guess: Every 5-10 years (as it looks none of them are gene thereapies), depending of lifestyle and specific rate of damage of the individual starting around ~30.
Wonder how long they'll last...
the whole point of these spin-offs is that the majority of them will not survive. there are a lot of ideas around aging and it’s really easy to get carried away to the point we throw everything against a wall and see what sticks.
kresten(2)
I'm interested if there is much anti-longevity sentiment here. I admit I'm very much against further moves to artificially increase human lifespan.
Am I quite alone in this?
Am I quite alone in this?
You're definitely not alone - though I disagree with your view, I've been in enough back-and-forths about it on HN to know that plenty of thoughtful people here are against life extension, for various reasons (that can't all be just reduced to Stockholm syndrome).
For instance, there's worry that life extension will vastly worsen economic inequality. Another problem is that a lot systems in society (e.g. retirement, insurance) is implicitly based on current average lifespan, and a sudden extension of it could cause such shockwaves in the economy that it would create more suffering than it would save.
I mention these two because I acknowledge them as real risks, but despite them, I'm 100% in support of life extension. I sincerely hope that one day humans will be able to extends life indefinitely, while retaining full capacity (i.e. no everlasting life in a body of a 90-years-old).
For instance, there's worry that life extension will vastly worsen economic inequality. Another problem is that a lot systems in society (e.g. retirement, insurance) is implicitly based on current average lifespan, and a sudden extension of it could cause such shockwaves in the economy that it would create more suffering than it would save.
I mention these two because I acknowledge them as real risks, but despite them, I'm 100% in support of life extension. I sincerely hope that one day humans will be able to extends life indefinitely, while retaining full capacity (i.e. no everlasting life in a body of a 90-years-old).
Interesting. I'm also interested in how you imagine your indefinite life. Do you suspect that whole new avenues of existence and thought will open up? Or do you view it as essentially more and better of the same?
> Am I quite alone in this?
I sure hope so.
But, to take your line of thinking further, what are the odds that we are currently at just the right lifespan for humans? If you are against increasing human lifespan, you should also probably be in favor of decreasing it, unless you think we are at very special point in time in entire human history.
I sure hope so.
But, to take your line of thinking further, what are the odds that we are currently at just the right lifespan for humans? If you are against increasing human lifespan, you should also probably be in favor of decreasing it, unless you think we are at very special point in time in entire human history.
I think the number is possibly arbitrary. I am not making any argument about it. I am just at present trying to understand why temperamentally and instinctively I am against it.
I am also seeking to understand if others feel as I do on this subject.
I am also seeking to understand if others feel as I do on this subject.
Dying was Impossible to evade so far. So the best thing for happiness and Mental Health is to accept or not think about it. Maybe even see it as a "good" thing
To even Aknowledge that it might be possible could lead to false hope and disappointment. I think thats the main reason many people are instinctively against it
The mind basically tries to protect them from fighting against the impossible and earning nothing but dread and disappointment.
To even Aknowledge that it might be possible could lead to false hope and disappointment. I think thats the main reason many people are instinctively against it
The mind basically tries to protect them from fighting against the impossible and earning nothing but dread and disappointment.
Not sure if same but I am in favor of artificially controlling age so you can decide how long you should live.
No. In fact I suspect my feeling is that control is exactly what is not good for humans to have too much of.
I think the opposite. I believe a lack of control, especially over one's mortality is what leads to a lot of the bad shit that happens in the world. If everyone was guaranteed their health and freedom from the shadow of death we'd probably be a damn site happier and less neurotic.
or freedom from the chains of living. It would be interesting to see how everyone reacts to an instant death switch or ability to set your own death date lower or higher than your natural life expectancy without society having control over it. Not only people want control over their lives but once they get it, they will naturally want to control others.
What if advanced medicine can extend your life beyond your natural life expectancy (maybe even immortality) but you don't want to live that longer?
Why isn't it always a good thing to cure people and prevent them from dying as long as possible, John?
Religion perpetuated the notion that living is inherently better than death despite suffering and we are stuck with it everywhere.
Rationally, is it true that someone can be better off dead? No. For something to be better, it requires comparison of former with later state. Since you won't exist, there is no state to compare. No one dead can feel sadness. (of course that's relying on there being no after life or reincarnation)
Flip that switch, is it true someone can be better off living? No. For the same reason, you have to presume continued existence is good since you can't rely on comparing states.
How do you know continued existence will be good or better?
That you can't. You can make a guess based on data relying on hedonism but that's all there is. No one agrees on what good continued existence is either so people in part are using their experience and values to judge which doesn't make sense if you allow individuals to have freedom of deciding their own values and life.
I say, we stop extending life expectancy and focus on cutting off the problems that make existing existence a pain even if for majority, happiness or society outweigh it. There are many useless things people waste their life on currently, why do they need to?
Religion perpetuated the notion that living is inherently better than death despite suffering and we are stuck with it everywhere.
Rationally, is it true that someone can be better off dead? No. For something to be better, it requires comparison of former with later state. Since you won't exist, there is no state to compare. No one dead can feel sadness. (of course that's relying on there being no after life or reincarnation)
Flip that switch, is it true someone can be better off living? No. For the same reason, you have to presume continued existence is good since you can't rely on comparing states.
How do you know continued existence will be good or better?
That you can't. You can make a guess based on data relying on hedonism but that's all there is. No one agrees on what good continued existence is either so people in part are using their experience and values to judge which doesn't make sense if you allow individuals to have freedom of deciding their own values and life.
I say, we stop extending life expectancy and focus on cutting off the problems that make existing existence a pain even if for majority, happiness or society outweigh it. There are many useless things people waste their life on currently, why do they need to?
Love of life is not the same as fear of death. If the latter is what drives the search for longevity then it will never be enough. So long as longevity isn't used to find peace with life and death, and transcend our limited perspective on life then I see it as just a frantic attempt to delay the inevitable. Resisting death at 150 will be just as painful as resisting it at any other age. If on the other hand it will give people more time to gain wisdom and perspective on what life is about then that's a whole different story.
Assuming it's like any other product or service, the people that implement longevity (if they do) will be a tiny fraction of the general population, and certainly not a random sampling thereof. Most people who end up being able to make use of longevity treatments will have had nothing to do with those who implemented them (except by working for company A which made product X which was used by company B to make ... which was one of the components the longevity researchers used); I think it'll happen regardless of their opinion about it (well, I guess if they violently opposed it, maybe they could stop it).
So, it's less a question of what drives the search for longevity than what we'll do with it once it arrives.
So, it's less a question of what drives the search for longevity than what we'll do with it once it arrives.
To touch on a couple of the other points that have been raised here, no our drugs aren't enzymes. We at SENS were working on an enzymatic approach for many years. There is still potential to engineering enzymes for this, but I designed our cyclodextrins to be a faster/cheaper/easier path to the clinic. Well, not that much cheaper. It's still very expensive. And yes, we are well aware of the hearing loss issue. It's avoidable, we believe we understand what caused it, and we're engineering around it. We'll be able to test whether we are successfully avoiding hearing loss in a very sensitive system in the next 9 months.
How long will we last? 16 more months with our current funding and burn rate. By then we need to have moved into series A so if anyone has any pharma VC contacts I'm definitely looking for warm intros :)