One of the things that rarely makes it to the press is that all of these efforts are not equal in their likelihood of producing therapies that are useful for old people.

A good 95%+ of the funding and interest in aging at present still goes towards investigation only, no attempt or thought on therapies. The Ellison Medical Foundation fell into this category, as aging was only an incidental part of the Foundation's plan. The point was molecular biology, and aging just happened to be one of the better fields to exercise that goal. So the EMF simply expanded some of the NIA study programs and arguably did nothing meaningful to advance progress towards therapies for aging.

Then 95%+ of the sliver of funding and interest that does aim to extend life goes towards things that have absolutely no hope of meaningful results. They are generally focused on trying to understand metabolism sufficiently well to slow aging slightly. An over the top ambitious goal in this area is adding seven years to life spans over the next 20 years - that's the Longevity Dividend proposal. There is no concrete plan, nowhere near the level of understanding needed to even have a plan, and so people pick at proteins and mechanisms one by one that might be linked to calorie restriction or autophagy or other longevity-associated mechanisms. Look at the past fifteen years of very expensive and entirely fruitless sirtuin research to see how this will go over the next decade. The research community is gearing up to spend billions more on mTOR-related work, and the expectation of outcomes should be exactly the same: knowledge, but not therapies.

Genetics is another area of favor at the moment, but is just another facet of "let's mess with metabolism" to try to find ways to slow down the accumulation of damage in this vastly complex poorly understood system. There is an argument to say that all of this focus on things that won't really help much is in fact just a new way for researchers to draw in new funding to the established goal of mapping metabolism.

Since aging is damage, slowing damage is pretty useless for old people. They won't benefit from that approach at all. If we're going to wait around for the next few decades for treatments, I want to see rejuvenation at the end of the line instead of merely tinkering the system to damage itself more slowly. Rejuvenation means repair: if aging is damage, then rejuvenation is repairing that damage.

So the vast unknowns in aging are not related to the actual damage itself, but rather how the damage interacts and progresses in the highly complex apparatus of our biology. There is a very good catalog of the biochemical damage that causes aging, the direct results of the correct operation of metabolism, not caused by other forms of damage. This is the list of distinctive differences between old tissue and young tissue. That catalog was built over the past century and hasn't been expanded since the late 1980s, so it is reasonable to think that all the important stuff for now is captured.

We could bypass the vast complexity of the "mess with metabolism" approach to slowing aging and instead try to repair the damage. This is much better as there are concrete plans for doing so, and so much is known of the damage that there are numerous very detailed proposals for producing repair therapies. If you can repair the damage then you don't need to know how it progresses in detail from moment to moment, or which form is more important, or how exactly it causes age-related disease. Just fix it. The analogous situation is rust in an ornate, complex, load-bearing metal structure: rust is simple, the structure is complicated, so the results of rust over time will be very complicated. Do you build models and analyse the molecular progression of rust in ever more detail to figure out how to build better structures, or do you just paint the thing and rustproof it every now and again? One of those paths is clearly better than the other.

This is why I don't expect great things from Calico, as Calico is funding the same mainstream approach to aging (mess with metabolism, drug discovery, try to slow aging) that will do a lot for knowledge and next to nothing for practical outcomes to extend life and rejuvenate the old. They won't fund the right path, which is to say SENS and related repair-based approaches, until those approaches have completed their disruption of the aging research field and gathered sufficient support that no-one has to specify repair-based approaches as being their approach, because it is just assumed that that is what is meant by aging research.