The other day I was asked about the role of denaturation of a particular protein in aging. It was a typical question that pretty much sums up the problem we have had in understanding (and doing anything about) aging during the past century. The problem is the question hides a flawed premise. It presupposes that […]
21st Century Science: Isn’t It About Time?
The other day I was asked about the role of denaturation of a particular protein in aging. It was a typical question that pretty much sums up the problem we have had in understanding (and doing anything about) aging during the past century. The problem is the question hides a flawed premise. It presupposes that molecules simply sit around and accrue damage. Put another way, the problem is that we look at molecules as part of as static pool rather than looking at the dynamic turnover that is the hallmark of metabolism.
Imagine a 1930 Duesenberg that has been lovingly cared for and is in pristine condition, even though it rolled off the assembly line 85 years ago. Compare this to my two-year-old car that already has a few rust spots. Was the Duesenberg better made than my car, that is, did it come with “better genes”? Was the Duesenberg exposed to less damage than my car, that is, did it have “fewer free radicals, less denaturing of its proteins, or a smaller rate of cross-linking”? No. The difference between that “ageless” Duesenberg and my own “aging” car is not the quality of the production line nor the exposure to sun, snow, salt, and dirt. The difference lies exclusively in the dynamics of its care. That Duesenberg was polished, aligned, oiled, repainted, repaired, and “recycled” on a regular basis. My own car is “aging faster” because I don’t care for it as frequently or as carefully as did the owners of that Duesenberg, and therein lies the entire difference between young organisms and old ones.
In aging organisms, it’s neither the genes nor the damage, but the slowing rate of recycling and repair that results in old cells, old tissues, old organisms, and age-related diseases.
Bizarrely and ironically, most people still look at biological systems and ignore the fact that they are alive, that they are dynamic, that they are constantly in flux. We look at a particular molecule – whether beta amyloid, collagen, GDF-11, or a thousand others – and we ignore the fact that these molecules are constantly being created, broken down, and replaced, but instead, we blindly focus on the damage itself. It’s true that as an organism ages any given pool of molecules shows an increase in damage – such as the aggregates of beta amyloid in early plaque formation – but the key is not the damage, the key is the slowing of the metabolic turnover. An accumulation of damage is not static and passively accumulative; it occurs because the rate of turnover falls as a result of changes in the pattern of gene expression. Whether we look at tau proteins, elastin, or any other molecular pool you want to look at, the key to the problem lies not in any particular gene nor in any particular source of damage. The key lies in the rate at which both anabolism and catabolism are replacing those molecules.
We don’t age because we accumulate damage, we accumulate damage because aging permits damage to accumulate.
A doctrinaire attention to “aging genes” and a catalog of one’s favorite sources of molecular damage will never result in cures to age-related disease. The key to intervention lies in the rate of molecular turnover, which responds to changing patterns of gene expression. Those who focus on genes and damage, to the exclusion of molecular turnover and gene expression, are perhaps some of our most highly-educated and intelligent minds of the 20th century…
…but it’s now the 21st century.
It’s time we caught up.