As I pointed out over at the Longevity Meme this morning, some exciting news materialized over the weekend. Researchers have apparently halted an important biochemical aspect of aging in liver tissue, and have the measurements of liver function to back up that claim:
The cells of all organisms have several surveillance systems designed to find, digest and recycle damaged proteins. ... One of these surveillance systems - responsible for handling 30 percent or more of damaged cellular protein - uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone ferries it towards one of the cell's many lysosomes ... Dr. Cuervo found that the chaperone surveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins. Could replenishing lost receptors in older animals maintain the efficiency of this protein-removal system throughout an animal's lifespan and, perhaps, maintain the function of the animal's cells and organs as well?
Yes, it could: the researchers demonstrated old mouse livers functioning as well as young mouse livers. On the one hand, this is solid support for a range of scientific initiatives aimed at lysosomal issues and buildup of damaging material in cells. For example, the work of the Methuselah Foundation under the LysoSENS program. On the other hand, this result suggests that - in the liver at least - the problem simply goes away if you deal with the missing receptors. This is interesting, as I was under the impression that a large portion of the issue in old humans stemmed from material that would never be broken down - the human lysosome just doesn't have the tools for the job.
This work on liver function was performed in mice; will this same sort of result hold in longer-lived mammals? We humans have tens of mouse life spans in which to build up even more impressive collections of gunk in our cells. Work on AGE-breaker drugs has demonstrated that old rodents and old humans don't necessarily have a lot in common when it comes to what sorts of biochemical gunk predominantly cause degeneration:
There are many, many different types of AGEs, and researchers have no exhaustive catalogue of them all; any given AGE-breaker is going to tackle one subset at most. Alagebrium most likely attacks a type of AGE much more common in old animals than old humans, for example - which is why it works so much better for rats than us.
Well, we shall see. I can't imagine the scientists failing to find funding to continue this line of research in one form or another.
One last item that caught my eye today was buried at the bottom of this article:
In research yet to be published, Cuervo has found that calorie restriction prevents the age-related decrease in [the chaperone system].
It's quite uncanny to see calorie restriction beneficially affect every new measure of age-related change and decline, even when that is what I'd expect based on evidence to date.