Recently Published: Why We Age

The programmed aging camp of aging research is a sizable minority in the field, and its members theorize that aging results from an evolved program of changes in metabolism, gene expression, and so forth. Some even think that aging processes are actively selected for rather than being a result of antagonistic pleiotropy, which occurs when a mechanism beneficial in early life is strongly selected despite the fact that it becomes harmful in later life. In later life the members of a species are no longer subject to the sort of evolutionary pressures that would lead to a better outcome for individuals. At the high level evolution only selects for reproductive success: the fate of individuals becomes irrelevant when they age beyond the point of providing meaningful contributions to the success of their offspring, and thus there is no further selection for sustaining, health- and longevity-enhancing adaptations.

Like the other big camp in aging research, the camp of those who theorize that aging is the result of a stochastic accumulation of damage to cells and molecules, programmed aging is divided into (a) researchers who think that there can be rapid progress towards radical extension of healthy life span, (b) researchers who think that only modest gains are plausible, and that even those will be hard to achieve, and (c) the silent majority who focus only on investigations of aging, not actually doing anything about it. The programmed aging approach to building therapies for aging involves altering gene expression and protein levels with the intent of changing the behavior of cellular machinery so as to turn back its operation to a more youthful mode. The researchers are often interested in furthering ongoing drug development programs such as investigations of rapamycin, as using drugs to enhance or suppress levels of specific proteins connected to aging is a step forward to their eyes, one that should lead to more sophisticated manipulations of the aging program in the future.

If you are in the aging as damage camp, as I am, this all looks like the slow road to nowhere, however. The cart is before the horse: damage causes change in gene expression and metabolic operations, not vice versa. This is an important distinction to make, because the research and development strategy that works well in a world in which aging is damage works poorly in a world in which aging is an evolved program - and vice versa. Thus one of these groups is achieving little other than to expand our knowledge of biology and aging.

In any case, this recently published book, while written from a programmed aging perspective, comes recommended. The interesting thing about the divide between the programmed aging and aging as damage camps is that their members largely agree on all of the fundamental observations and science of aging as established to date - the facts are what they are, and the difference is all in the interpretation of those facts. The book is an easy read, aimed at the layperson, but still educational, and the author holds that agelessness can be achieved in the decades ahead with sufficient funding of suitable research programs. I'm always pleased to see more people in the community espousing ambitious views, as ambition for radical change is the first step towards actually making progress.

Why we age: Insight into the cause of growing old

Why are we mortal? What are the causes of aging, and how, if at all, can the process be halted? The issue of aging, which so thoroughly consumes our youth-loving culture today, has only gained traction in the last century. Prior to this, disease, accident, or other misfortune caused the majority of deaths, rather than the effects of old age. As medicine advanced, vanquishing many diseases and adding decades to life expectancies, so old age and the natural shutting down of the human body became a trial for all to bear.

Dr Walker brings to light a real possibility in this age of advanced scientific prowess: the extension of the biological human lifespan beyond its current natural limits. By examining the aging process, scientists can isolate what causes our bodies to age, and therefore, also learn how to control this mechanism. Dr Walker believes that we could be seeing huge advances in this area before the end of the century, and here he explains why.

The book is organized into sections which each deal with a specific theory or question of aging, progressing historically through the often misunderstood relation between aging and death, the effects of aging, the theories on why we age, and ending with a tantalizing glimpse of a future without aging. Dr Walker takes a measured look at these complex issues, giving weight to each discussion with key evidence from several scientific fields. He discusses how "biological immortality" could be possible, by systematically examining evidence and theories to show why this concept could be achievable sooner than we think. The book is not designed as an academic thesis; rather, it is aimed at the average reader keen to understand their own experiences of aging and learn about the exciting advances scientists are making into this field of research.

I notice that Aubrey de Grey wrote a short review:

Although I myself am a proponent of the current mainstream view that aging is a non-programmed, damage-driven process, and I dispute Walker's arguments in this book for rejecting that view, I nonetheless believe that the book has great value: firstly because the model set out here is not one that I believe can be rejected out of hand, secondly because in the event (however unlikely in my view) that it is correct it would point the way to a far simpler and more easily implementable approach to medical postponement of age-related ill-health than would otherwise be available, and last but by no means least that the book is extremely well-written for a general audience, expounding in highly accessible but yet detailed terms a wide variety of aspects of this fascinating and vitally important field. I therefore recommend this book to anyone who is seeking a basic introduction to the biology of aging.

If aging is accumulated cellular or genetic damage, why does aging have three speeds? If using lipofuscin, accumulated cellular debris, as a marker of aging, then there is little to no lipofuscin during growth years, progressive lipofuscin accumulation in middle age and a flattening of lipofuscin buildup in the late years of life. Upon examination, lipofuscin accumullates when organelles inside cells called lysosomes cannot efficiently clean up cellular debris enzymatically. This dysfunction occurs as metallic minerals accumulate (iron, copper, calcium mainly). Then mineral chelators could reverse biological aging by mopping up excess minerals. A few experiments show this is a valid hypothesis -- over mineralization drives the speed of aging. Calorie restriction largely works by limitation of mineral intake, not calories. The eradication of lipofuscin at the back of the human eye has been directly observed with use of mineral chelators. In order to proceed with anti-aging strategies, a theory of why humans age must be developed. Epidemiology backs the idea of overmineralization as countries that have grasslands and water have cattle (steers and cows) and consume the most calcium from dairy and iron from red meat (Scandinavia, Ireland, North America, New Zealand) and have the highest rates of heart disease and cancer in the world.

Posted by: Bill Sardi at October 20th, 2013 11:27 AM

Excess iron is known to cause diseases of aging. Calcium requires vitamin K2 to get where it needs to go, and K2 production declines with age. Calcium in the wrong places is also known to cause diseases of aging.

But those aren't the only kinds of damage, and preventing over mineralization won't stop you from aging or make you immortal. So don't get so attached to one category of damage that you forget the others.

The SENS Foundation has made excellent progress removing lipofuscin from the back of the human eye without using metal chelators, and I think their method will be safer.

I think it's other kinds of damage that affect the rate of lipofuscin accumulation. Mitochondrial damage being an obvious candidate. Existing lipofuscin accumulation probably also makes it harder for the lysosome to break down things it normally can, causing a speedup until it fails completely.

Posted by: Carl at October 20th, 2013 10:13 PM

Regards programmed versus damage. Keep in mind that we humans got radical life extension of multiple decades more than a doubling of lifespan from the great apes with minor gene tweaking as we're more than 95% the same. Drugs can tweak gene expression substantially, so getting at least a few more decades, shouldn't be out of the question of theoretical possibility.

The other thing is regards the negligible senescence species, we need sequencing and comparison to tell. But It's my belief that it is highly unlikely lots of additional complex repair mechanisms have been added. I believe that existent mechanisms from their aging ancestors, like those that export molecular garbage have likely been ramped up to high enough levels.

Posted by: Darian Smith at October 21st, 2013 3:00 PM

"Calorie restriction works largely by limitation of mineral intake"

Bill - What's the evidence for this? Has anyone done experiments reducing mineral content of mouse feed, putting them on a high-calorie, low mineral diet?

Posted by: Josh Mitteldorf at October 22nd, 2013 10:59 AM

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