Fight Aging!

If it's become so glaringly obvious that aging is the key reason behind something like heart disease, why aren't more scientists and regulatory bodies acknowledging it and trying to attack the root cause (aging)? I know support is building on that end, but it's not fast enough, and there is so much money being spent on trying to treat things individually as opposed to going after the root cause. It's frustrating to see so much money being spent on something that will likely not produce great results.

To add:
I know a lot of these companies who are researching and developing drugs are risk adverse, but if the consensus keeps building that aging is the key factor, it seems like they're just spinning their wheels working on individual diseases. I know the regulatory system is brutally tough, and hard to change, but what am I missing here? Or do a majority of scientists think that aging isn't the cause of most of these diseases?

It's not at all clear that getting researchers to think about aging as a root cause of disease will lead to a huge amount of progress. It might even be harmful, since they may look at what mainstream gerontology recommends (i.e., slowing aging instead of curing disease) and pursue that rather than SENS which is still sort of fringe. In the case of heart disease, they just need to find effective ways of getting rid of crosslinks, plaque, and amyloid (I doubt that senescent cells and stem cells play a big role in HD).

So, why hasn't heart disease been cured yet? Major reasons include that the world's top experts on glucosepane think that getting rid of it is physically impossible and the SENS approach of eliminating plaque has remained obscure (this shouldn't be too surprising: lots of good ideas remain unknown for long periods of time). I'm less sure about what's holding up amyloid clearance for HD. Maybe HD researchers are waiting to see what happens with the amyloid-clearing strategies for AD before they become involved.

Will SRF apply for this grant?

@Ham: I guess most scientists don't think we can do something about aging. And even those that do think so, only aim to slightly slowing aging.

Antonio, I was under the impression more and more were coming to the realization that something could be done about aging. Perhaps it's sensationalist reporting that gives me that impression then, because there certainly is a lot of that out there. You do see more and more scientists saying the current method of attacking one disease at a time is ineffective and needs to change though.

Do you think their goal of only slightly slowing aging is something that they say in order to not lose credibility, or do you think that's actually all they're shooting for? The metformin trial team for example was very careful to make sure they did not talk about "anti aging" or "life extension" in their pitch to the FDA, and chose the compression of morbidity approach.

Florin: Glucosepane does seem like it's going to be one of the larger challenges, for sure. Do you think the SENS type approach for glucosepane seems promising in the long term? As far as the current trend of gerontology, I'd like to think that view is hopefully changing. Especially with the recent money being put into the field with things like Calico, and HLI (despite speculation here about what will come out of it, it's probably helpful regardless) aiming to do better. I wonder if having a giant company like Google involved in the field will be beneficial in getting the ball rolling with the governments and regulatory bodies, given all the clout they have here?

@Florin - which experts think Glucosepane cross link removal is impossible?

I don't think I should mention anyone by name in this case. Ask Aubrey if you're still interested.

@Florin - could it just be that Glucosepane is a good idea that just doesn't really have the tools and support community around it for labs to take a look at it? I've been following the DRACO Indiegogo campaign, and it seems that the only major reason why no one is that interested in it, is that not enough basic research has been done yet, a pretty maddening situation for those scientists interested in pushing it forward.

https://www.indiegogo.com/projects/dracos-may-be-effective-against-all-viruses#/

Yes, Jim, that might be part of the problem and part of the solution. But why doesn't the mainstream fund the basic research stuff on its own if it's so promising from a theoretical perspective? I've asked myself and others that question, and for me, it seems that there's no single or simple answer (maybe apart from glucosepane). There's a bunch of possible reasons that prevents funding for some SENS approaches while other reasons conspire to fully fund others like beta-amyloid vaccines and stem cells.

"But why doesn't the mainstream fund the basic research stuff on its own if it's so promising from a theoretical perspective?"

Good question. I read a statistic somewhere that 90% of drugs that enter clinical trials fail by stage 3, and I suppose that is not because their 'target' wasn't promising, but is because they have unintended side effects, or are just not effective like they where in vitro and in model systems. Viewed like this drug development is a very expensive lottery.

I'd also guess that like Glucospane, lack of basic tools can hold a field back.

Why the "Valley of death" exists is obviously a lot more complicated than that though, and I am only a layperson guessing. I don't even know if I've covered all the reasons.

Ham, I've heard that there are certain ideas that the glucosepane experts haven't considered that might be worth trying. And in any case, there aren't any good alternatives than to try really hard to breakup glucosepane. Perhaps replacing all of the tissues in which glucosepane accumulates would be a way to get rid of it, but that would be extremely expensive and invasive and might not even work if glucosepane accumulates and has negative effects directly inside the brain.

I'm not too excited about Calico and HLI. As you may know, Aubrey claims that Calico and HLI has made his advocacy job easier, but this doesn't seem to have translated into significantly more donations for the SRF or for funding of SENS approaches in general. As for the orgs themselves, HLI seems obsessed with hypeomics which is unlikely to cure anything, and Calico so far doesn't seem inclined to pursue any sort of SENS approach, if their partnerships and hires are anything to go by. So no, I don't see much change in gerontology or in large, private-sector-funded research efforts.

During one of his AMA's Aubrey said he would like to collaborate with Calico, which I think would be nice, even if it were operating as a branch under the Calico umbrella or something along those lines. As far as making Aubrey's advocacy job easier, you'd be surprised how often people on places like reddit tend to just take the "don't worry, google is on it" attitude, like there's been tons of breakthroughs, and the road goes through Calico only. We still need more SENS advocacy for sure.

We may not like the approach that Calico or HLI have been taking (that they've announced so far... we really don't know too much about Calico's ultimate end game and future partnerships), but like I said earlier, my hope is that they get the regulatory bodies to rethink their stance on aging, seeing how they're both looking to develop interventions for it. More-so than the metformin group. It would be unfortunate for them to spend all this money only to be told they can't pursue whatever drug they might find. But anyway, if looking at the current partnerships that Calico has made is an indicator, then no, they aren't really pushing too many SENS types approaches yet... Which is disappointing for a company like Google, who normally does things a little bit out of the box. I have a ton of questions as to why more people aren't pursuing the SENS type rejuvenation approach, but most of them have been talked about ad nauseum anyways. I still remain hopeful about Calico though, but I don't know what to think about HLI. I certainly admire Venter and won't completely discount them.

I'd still like to see followups and advancements on the Senolytics that were discussed earlier in the year. Would be mighty promising if those came to fruition for sure.

Florin, could it be that Aubrey meant he now can quote more "visible" institutions as attempting to tackle ageing too, thereby demonstrating that he's isn't a lone looney?

Probably, but as I mentioned before, it doesn't seem to have made much of a difference to the bottom line, i.e., SENS funding. It might even generate complacency by leading people to think that since Calico, HLI, and others are tackling aging, they don't need to get involved. Time will tell, of course, but right now, it's not looking good.

Ham, I agree that SENS advocacy is necessary to at least keep the low level of funding that the SRF is getting today from disappearing entirely, but I doubt that it will increase SENS funding by millions directly.

I have a bit of hope that Calico may adopt some sort of SENSibe strategy in the future, but HLI probably won't, since Venter is a genomics guy. Currently, small private orgs and gov-funded projects (senescent cell clearance as you mentioned, and thymus rejuvenation is another example) are adopting more SENSible approaches for the neglected areas of SENS.

As for defining aging as a disease, I don't think it's something we need to be too concerned about.

Florin, even if Google and HLI are involved, it won't be nearly enough to move the masses until, say, all the first SENS mice have formidably outlived their normal kins and newspapers around the world made headlines about it.

Or skins can be visibly rejuvenated; and people will suddenly stop wasting their money in cosmetics.

But at least for now it helps back up Aubrey's vision. It's a double edged sword though, as it could indeed generate some complacency.

Yeah, but to get to even RMR you need a heck of a lot of dough. This is the classic chicken and egg problem: the public won't donate much if you don't have RMR, but you need the public to donate a lot to get to RMR. And I'm also kinda skeptical about the impact of RMR itself; it seems that claims of rejuvenated mice are a dime a dozen today, yet the public is still apathetic.

There's one way to get SENS fully funded without much public support: having some sort of IP transfer and getting paid a lot for it. That's hopefully what will happen with SRF spinoffs such as HRT.

I think most people either don't care, or are just tired of hearing about mouse studies and want to see results in humans. I know the mouse part is a necessary thing, but seeing translatable results in humans is when the attention, and money should start flowing.

@ Ham - that is why RMR should be just a step into the process, and then move on as fast as possible. There are tons of things that will not translate between RMR and human studies. However most of the people on this blog make RMR a cornerstone, while in fact giving to it too much attention will introduce an unnecessary loop. Try to convince SENS people about this ... good luck.
And yes, mouse studies are nice, but they will answer couple things, while open up many more. Definitely we need DARPA more involved in rejuvenation technologies.