Michael Fossel Michael is President of Telocyte

December 31, 2015

A Gerontological Reality

An odd thing came across my desk yesterday: a reminder that some people, without meaning to, encourage not only a sense of futility and gloom, but in their dark view of the world, they end up encouraging disease, including Alzheimer’s. In the middle ages, it was common to attribute disease and suffering to god’s will and, after all, who were we to intervene in what god intended? Labor pain, plague, and a myriad sufferings were – again with a sense of futility and gloom – accepted and instead of encouraging our fellow human beings to alleviate suffering, we actively suppressed the compassion that might have brought relief.

Now, we look back on the misguided superstitions of the middle ages as something we have – in our maturity as civilized human beings – outgrown. And yet, we haven’t grown up enough, for while we no longer blame god for our troubles, we are just as eager to ensure that we can’t solve them. In my recent book, The Telomerase Revolution, I suggested that not only could we cure Alzheimer’s disease and that we could make such care affordable, but that it would be more affordable than our current health care, both for the individual and for society. Far from being a treatment for the few, it would be a treatment for all. After all, why pay enormous costs for long-term nursing home care, when we could pay a small cost to be healthy? Far from further dividing us into “two kinds of human beings” (consider that we currently divide the old and the infirm, or those with Alzheimer’s, from the young and healthy), we could provide the gift of sanity and health to all of us, without regard to age, without regard to wealth.

The consequence? A healthier, more compassionate culture.

If this is a utopia, the it’s not the first one. Prior to the discovery of antibiotics, prior to the availability of insulin, prior to polio vaccine, each of these ideas were utopian, yet now they are merely reality. Or perhaps not merely, for these utopian medical advances saved lives. Oddly though, we have never lacked for naysayers, who once – as they now do for Alzheimer’s – view these advances with fear and trepidation, seeing not the joy, the love, or the improved health, but the “ruin of their hopes in an utterly alien world”. How does curing polio ruin hopes? How does curing Alzheimer’s give us an alien world? The ruin of hopes, the alien world is the world that Alzheimer’s patients live in now, along with their families who watch the premature loss of their loved ones (of which there are already far too many). Would anyone really want to live in a world without Alzheimer’s? Yes, most of us hope for exactly such a “utopian” world and some of us are working hard to make it a reality. Curing Alzheimer’s is an attainable dream, not a utopia and most certainly not a dystopia.

May you all have a happy new year, and may the coming years soon see a future beyond Alzheimer’s disease.

December 21, 2015

Alzheimer’s isn’t just forgetting, it’s forgetting our assumptions

The rate-limiting-step to innovation is assumption.

Often, we have the infrastructure, the knowledge, and even the intelligence we need to move ahead, but stumble and fall over our own assumptions. Why didn’t Europe use immunizations hundreds of years earlier than it did? Why didn’t we discover – and make use of – the steam engine in ancient Rome? Why did flight, electricity, or sailing ships come about when they did? Why not earlier? Occasionally, we lack a critical piece of technology, one that slows us down for decades or even centuries. Occasionally, it’s an odd piece of data, a fact, a small subset of knowledge.

And sometimes, it’s a simple lack of intelligence: we simply aren’t very smart.

One key to being not-being-very-smart occurs when we make the wrong assumptions. Again and again, we misunderstand the nature of reality, while assuming that we already understand completely. Physics was all but certain – just prior to the end of the nineteenth century – that we knew all of physics except for a few niggling little details, but those “little” details left room for quantum physics and, ultimately, an electronics revolution, hence cell phones, the internet, computers, and computer blogs, like this one.

Assumptions have a way of limiting our vision. Obviously we can’t fly because, after all, how could something heavier than air possibly stay up in the air? Yet tons of steel and plastic manage that feat every day throughout the world. Obviously we can’t sail around the world because, after all, how could you avoid falling off the edge? Yet once again, the assumptions about “the world” were a bit off the mark.

Our assumptions about Alzheimer’s disease are – albeit with a desperately tragic languor – slowly beginning to change. The change involves a set of related, but slightly different assumptions, that are finally giving way. One assumption is that beta amyloid and tau proteins, are the cause instead of a result. Another assumption is that the cause lies within the neurons, which are merely innocent bystanders. We likewise assume that the cause lies in the genes, looking harder and harder in the wrong location, while ignoring the role played by changes in gene expression. A final assumption is more subtle: when we look at pools of molecules, such as beta amyloid, we look at them as a static accumulation of damaged molecules. We completely ignore the hallmark of biological processes, the dynamic turnover of all such pools. We then go on to focus myopically on the damage and completely ignore the broader and more critical question: why does molecular turnover slow down as we age, thereby permitting the damage to accumulate in the first place?

Today’s new federal budget has a 60% increase in funding for Alzheimer’s research, bringing total funding ($936,000) to just short of a billion dollars. Next year’s NIH budget also calls for just short of billion dollars ($961,000) for Alzheimer’s funding. Given the money going into Alzheimer’s, the risk is not that we lack funds, but that we lack insight. We will be funding research on sensors, biomarkers, and nursing care. Of the money that goes toward finding a cure, some will be aimed at sleep quality, diet, inflammation, and genetics. But how much of this will be – ultimately – fruitlessly spent on projects that don’t cure Alzheimer’s disease? We need to spend, but spend wisely. Throwing money does not per se conquer a disease that steals the minds and souls of those we love. We need to throw it accurately.

We need to reassess our assumptions and look, very carefully, at reality. If we want to cure Alzheimer’s disease, it will not be solely a matter of good intentions, political will, and funding. It will be because, finally, we chose to understand how Alzheimer’s disease works.

And we chose to cure it.

December 7, 2015

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.

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