Florin

Posts

Sorted by New

Comments

Why SENS makes sense

There's no compelling evidence that these kinds of mutations cause bad stuff to happen in a normal lifespan.

Why SENS makes sense

The point is that if the amount of tau/other junk could be kept low enough (by periodically removing it), then the accumulation of too much cytoskeleton damage should be avoided.

Why SENS makes sense

Cytoskeleton damage can be upstream/causal

Too much tau junk → too much cytoskeleton damage

Lipofuscin

Too much lipofuscin/A2E → AMD

what SENS does right now is not sufficient

That's LEV's job (SENS 2, 3, etc.).

If you still think that there's any potential primary damage targets that SENS doesn't specifically mention, please let me know.

Why SENS makes sense

I don't see how it would ever be physically possible to prevent every single lipid and protein from becoming oxidized or otherwise damaged in certain ways. And how will your enzymes prevent every single lipid and protein from ever forming aggregates? This seems only slightly less impossible.

Aubrey doesn't talk about immortality that much anymore and says that it's all about health, but that doesn't seem to have made much of a difference.

Why SENS makes sense

Spliceosomes are super-relevant too  given how they are upstream of everything else (William Mair has shown that dysregulation in these accelerates aging, and correcting the defects can up lifespan)

You can argue that "ER + aging", "golgi + aging", or any "cell process/component + aging" is going to cause some downstream effects on aging, and to fix everything, you have to "fix" the ER, fix the spliceosomes, fix the cytoskeleton, fix the golgi, fix the NPCs, fix the histones, whatever.

Yes, this can get tricky. Do you have to directly fix everything that goes wrong? If not, how do you know what damage to directly fix?

The stuff that needs to be directly targeted in the cell (ideally, before cellular structures are damaged too much) is damaged or aggregated lipids and proteins and mutations in the mitochondria. This is the primary damage that generates secondary damage to cellular structures (like cytoskeletons and nuclear transport systems). Mutations in the nucleus aren't targeted directly but are dealt with by WILT (or whatever could cure all cancer forever) and senescent cell killing via senolytics or whatever could get rid of them. So, fixing this primary damage should prevent most of the secondary damage from ever occurring, and if lots of secondary damage has already occured (like in older people), the repair of the primary damage may allow the self-repair machinery of the cell that still works to repair itself and the rest of this secondary damage.

Why SENS makes sense

This sounds like (or is) the TDP-43 and FUS aggregates gumming up the nuclear transport system that was mentioned earlier.

Why SENS makes sense

bowhead whales

birds

naked mole rats

more saturated cellular membranes...more resistant to ROS

deuterated PUFAs

protein variants expressed by centenarians

This is all messing-with-metabolism. How are you going to slow metabolism in humans? Supposedly, hyaluronic acid is what keeps naked mole rats from developing cancer. Do you think it would be a good idea to start injecting people with that stuff? Also, none of those animals avoid aging. Centenarians still age and die. More saturated cellular membranes and deuterated PUFAs might be more resistant to ROS, but that will only slow aging at best, not reverse it. There's just no reason to think that MWM could ever cure aging.

Protein traffic jams

isn't mentioned by SENS and can occur even w/o protein aggregates or lipofuscin

Actually, they occur due to TDP-43 and FUS aggregates gumming up the nuclear transport system. The SENS solution is to get rid of this aggregate junk, of course. These specific aggregates aren't mentioned by SENS, but they fit within the SENS damage category of "intracellular aggregates."

mitochondrial transfer

as an alternative to mitoSENS

Yeah, but what happens to the mutant mitos?

And in any case, this can be considered a different approach to MitoSENS, not an alternative. Yet another approach is the Shift effect. MitoSENS isn't wedded to the notion of copying non-mutated mito genes into the nucleus.

IPSCs and epigenetic/genetic reprogramming

iPSCs are useful for stuff like WILT and to replace cells that aren't so easily replaced in organs like the brain.

Transient reprogramming is also potentially useful, but more research is needed to determine whether or not it could lead to cancer.

glycosylation

This seems more like age-related changes in glucose and hormone levels that should return to normal once the relevant damage is repaired, rather than something for SENS to target directly, but I'll need to double check.

Why SENS makes sense

it's much easier to fix oxidative modifications

How are you going to be able to fix every single modification? That seems physically impossible. At best, you're only going to slow down the rate of aggregate formation, but aggregates will still accumulate and kill you.

200+ oxidative modifications

How many of those actually matter? I'd expect that most get degraded, and the rest float around doing bad stuff or form aggregates.

The scope of the aging problem is so vast

use all techniques

This would only matter a lot if you want to disentangle what metabolism is doing (which is vast) and try to get it to do the impossible: prevent every single lipid and protein from going bad. I doubt even an AI god could make that happen, nevermind mere mortals equipped with what amount to fancy expert systems.

Better tools help reduce the intense labor and time costs

Better funding is better than better tools. If SENS got $100 million per year starting in 2004 or even as late as 2010, we'd already have immortality in the bag or know that SENS couldn't deliver the goods and moved on to something else.

Why SENS makes sense

Cytoskeleton dysfunction is probably a secondary kind of damage (like stroke damage) rather than damage that SENS needs to repair directly: consequence rather than cause. It's associated with the accumulation of tau and other kinds of junk that cause neurodegenerative disease and with excessive oxidation and lower energy levels (both probably caused by mutant mitos). SENS already covers that stuff.

However, I've never heard of these Hirano body aggregates before, so I'll take a look at that.

Load More