Fight Aging!

The SENS Research Foundation coordinates fundamental research into the technologies needed for future rejuvenation treatments. There is in fact a very clear roadmap leading from where we are today to the means to repair the cellular and molecular damage that causes aging. Outside of stem cell research and cancer research, most of that roadmap is lagging far behind, however. There is little interest and little funding despite the fact that other causes of aging as just as important to the development of age-related disease as faltering stem cell activity and the conditions that give rise to ever higher risk of cancer with passing years. Thus the SENS Research Foundation staff aim to push past roadblocks and spur further progress where that progress is very much needed: in ways to repair mitochondrial damage or clear persistent cross-links from aged tissues, for example. These efforts are funded by philanthropic donations, so we get the progress we are willing to support. Certainly there is no other organization out there yet doing anywhere near as much to advance repair-based approaches to treating and reversing degenerative aging.

This month's newsletter from the SENS Research Foundation turned up in my inbox today. If that wasn't the case for you, you might consider subscribing or making a donation to help fund the important work carried out by the Foundation. The newsletter pointed out a short interview from late last year that I'd missed:

Q & A with SENS Research Foundation President, CEO and Co-Founder Michael Kope

SRF is a public charity, and we intend to transform the way the world researches and treats age-related disease, by promoting truly comprehensive regenerative medicine. The unique aspect of our work is our focus on a damage-repair paradigm, and we advance that with our own scientific research and with collaborative projects, conferences, events and education programs.

SRF supports three research projects at its Mountain View Research Center, and an additional fifteen projects at universities and institutes around the world. The list includes Oxford, Harvard, Yale, the Buck Institute and the Wake Forest Institute for Regenerative Medicine. The goals are as ambitious as removing the underlying causes of age-related diseases such as macular degeneration, atherosclerosis, Alzheimer's and cancer.

And we're not just research programs: educating the public, building a community of support, and training researchers to support a growing rejuvenation biotechnology field are also major endeavors of the organization. Our internship program is growing, our research advisory board is expanding, and rarely a week goes by without a speaking engagement or event on our calendars.

As is often the case the most interesting part of the newsletter is the Question of the Month section, which this time around looks what we know about cellular and molecular damage accumulation in very early life. While reading, it is worth bearing in mind that the application of reliability theory to aging best fits the observed data in models where individuals are born already possessing a modest but non-zero amount of damage.

Question of the Month #8: Aging Damage and Early Early Detection

Q: Because the cellular and molecular damage of aging is a by-product of metabolism, I have always assumed that it accumulates throughout our entire lives - from when we are a baby until we die. Is this true? Is there any research showing that very young children have low levels of tissue-stiffening crosslinks, extracellular aggregates like beta-amyloid, or intracellular aggregates (like lipofuscin or the ones driving atherosclerosis) in their tissues?

A: Scientists don't have any single, comprehensive answer to this broad question, in part because there hasn't been a systematic investigation into it, and in part because the answer likely depends on the specific kind of aging damage under consideration. To really answer it, one would need to begin an investigation for each aging-damage precursor by taking tissue samples from newborns, and then performing ongoing testing periodically throughout life. As a second-best, you'd do a cross-sectional study comparing neonates, five-year-olds, pubescent children, very young adults, and then adults, including ages spread fairly evenly across the remaining lifespan. It would be difficult to perform such studies both institutionally and technically, as they would be quite expensive and would involve sourcing tissue samples from individuals of all of these ages, acquiring consent to use them for studies, and securing funding to do all this.

From a technical standpoint, it is already difficult to quantify many kinds of aging damage even in older people. The extreme case here is the key tissue-stiffening crosslink glucosepane, which is very fragile when subjected to most laboratory tissue treatments and has heretofore needed to be painstakingly extracted from tissues using a laborious series of sequential enzymatic extractions. Happily, this is likely to change soon, thanks to excellent progress being made in research that SENS Research Foundation has been funding in the Spiegel Research Group at Yale for several years now, developing enabling technologies for the development of glucosepane crosslink breakers. And it is inherently even more difficult to probe tissue samples for aging damage in very young people, for the obvious reason that the damage is by definition present at much lower levels in very young people's tissues than it is in older people's.

What little data we do have on aging damage precursors in the very young comes, for instance, from autopsy studies of stillborn infants. All such infants have at least some lipid deposition in their arteries, with as many as 25% of them having the "fatty streaks" that are the first visible sign of accumulating foam cells. These early lesions are particularly common in infants born to mothers with high serum cholesterol. Children are also born with some mechanical fatigue and fraying of the complex, lamellar structures of the stretchy protein elastin that provide arterial tissue with its elasticity, and this damage progressively increases with age. And there is already crosslink damage in the trachea and the bronchi of the lungs of newborn rats.

It's important to remember, however, that from the perspective of developing the therapies we need to delay and prevent degenerative aging, it doesn't matter whether or how much of these various aging lesions are present in very young people. Whatever their level may be, and whatever their rate and mechanisms of accumulation, the aging damage that is already present in the bodies of young adults is clearly harmless at the low levels at which it's present, as evidenced by the (by definition) youthful good health that college students and thirtysomethings enjoy. It's only decades later, as the level of cellular and molecular damage in different tissues accumulates to a characteristic "threshold of pathology," that enough of a given tissue's functional units are disabled to overcome its evolutionarily-inbuilt redundance and meaningfully impair tissue function.

In order to restore and maintain youthful health and functionality, then, we don't need to eradicate aging damage from the tissues of aging people; nor do we need to begin treating healthy young adults to push their burden of aging damage down to levels typical of children. Rather, we only need to develop rejuvenation biotechnologies capable of periodically removing, repairing, replacing, or rendering harmless enough of a tissue's molecular and cellular damage as to restore its structural integrity to what it is in young adults - complete with its original, lower but nonzero level of damage. At that point, the rejuvenated body will be structurally and functionally young, and its metabolic derangements will be restored to health as a downstream consequence of the intrinsic order of the youthful body. With this return to normal functionality at every level will come restored health, vigor, and vitality that ongoing periodic treatment can maintain - for many years longer at first, and ultimately indefinitely.