Dear Future Centenarian,
People often ask me why I’m so confident we’ll be able to reverse aging in our lifetime. Let me use 3-D printing as an example.
I was less than ten years ago when the first bioprinting application was made. And only a few years ago that mainstream news started paying lots of attention to it. To this day, most have no idea what it’s all about.
This is the nature of and the rapidly accelerating trend of medicine. Disruptive technologies that hardly anyone hear about… and fewer dream about… suddenly burst on the scene and change the game forever.
Read the following from Reason at Fight Aging.com. What’s next? And what will follow that? Popular forecasts are made based on trends. Since most prognosticators are afraid to stick their necks out (Heaven forbid they make a mistake and look foolish), they stick to safe conservative predictions.
Meanwhile, world-changers quietly work away until they break through with technologies that upset the apple carts.
Here’s Reason’s take on this issue:
3-D printing is a tool that has blossomed given the cheap computing resources to control it. It has long been possible to print three-dimensional structures in a variety of mediums, but efficient automation makes it cheaper to do this reliably and repeatedly, and also allows for the accurate manufacture of objects with very small scale features.
Since cheap computing resources also drive progress in biotechnology, it is only natural that advances in tissue engineering go hand in hand with 3-D printing. These possibilities had to occur at the same time, as they depend on the same underlying technological capabilities.
Tissue engineers want the ability to produce structures that mimic the collagen scaffold of the extracellular matrix, webbed with blood vessels and all sorts of other structural features on scales varying from millimeters to micrometers.
As a goal that is yet to be achieved completely, but so far good enough attempts have been produced to create several less complex forms of tissue: a scaffold is printed and in the process of its construction is seeded with cells and proteins that encourage growth.
Researchers have been working with 3-D printers for some years now. Some of the formative research programs and first companies in the space are on their way to being a decade old, such as Organovo, whose founders count the Methuselah Foundation among their investors.
The focus today is still largely on the production of products for research groups, producing small tissue structures such as printed blood vessels that can speed up the research process. Later, we will see more in the way of larger organs and tissue sections printed for transplant, not research. That is not too many years ahead.
Print Thyself: How 3-D printing is revolutionizing medicine:
Central to the lab's work are three customized 3-D printers, each worth a quarter of a million dollars. Lewis led me through a warren of corridors and offices to a room where one of the printers sat on supports. It was immense.
The base of the printer was a granite block five feet long, four feet deep, and a foot high, weighing a ton and a half. The printer does such fine-scale work that a stable base is essential, Lewis said. Resting on the block was a flat stage or platform, above which, in a vertical row, stood four rectangular steel containers, each a foot or so tall - the ink dispensers.
A tangle of colored wires connected the dispensers to some machinery behind them, and each dispenser was controlled at the top by a robotic arm. To the side sat a large monitor and a computer, which controlled the printer.
Each dispenser contained a different biological material, Lewis explained. One held an aqueous suspension of chemically treated collagen, which serves as the matrix on which many of the body's tissues take shape. Two others held suspensions of fibroblasts, the gristly cells that form the body's connective tissue. The last dispenser contained the fugitive ink that Lewis had developed to create channels within materials.
On the computer, Kolesky called up a software program and found an image representing the block of tissue that he would be printing.
It looked like a rectangle of semi-clear gelatin, within which was a vascular network: a channel entered at one end and branched into smaller vessels, which looped around and ultimately joined back into a single vessel that exited at the other end. It was a simple network, approximating the way that an artery divides into smaller capillaries that eventually recombine into a vein.
The dispenser with the fugitive ink moved quickly and almost imperceptibly, releasing an exceptionally thin stream of what looked like agar onto the glass slide. The printer clacked and clattered like a busy riveting machine. In a minute or so, the job was done; the printer had left a trail of gelatinous ink that exactly matched the pattern on the computer.
The stream of ink was about a tenth of a millimetre in diameter, and the entire pattern covered an area a little larger than a matchbook. The printer wasn't rigged to finish the job, but Kolesky explained what would typically happen next.
The other ink dispensers would take their turn, laying down a lattice of collagen and fibroblasts that would solidify around the network of fugitive ink, encasing it in tan-colored living tissue. To drain the fugitive ink, Kolesky would place the tissue on a chilled stone cube; this would cause the ink to change from a gel to a liquid, after which he could then extract it with a small suction device.
The end result would be a block of living tissue suffused with intricate vessels capable of carrying nutrients to the cells within.
The last step was to me the most remarkable. Once the vessels were empty, Kolesky would take a suspension of endothelial cells - the cells that line the insides of blood vessels - and inject it into the vessel network.
The cells would settle in and multiply to line the insides of the channels, effectively turning the channels into blood vessels. And then the cells would spread - they would begin to branch off the existing vessels and form new ones. In effect, Lewis and her team have created an environment that the cells consider home - it is far more natural to them than a petri dish or the inorganic scaffolds that had previously played host to cultured tissues.
"I like to say that we design the highway and then get out of the way and let the endothelial cells create their own driveways," Lewis said. "It's better to rely on the intelligence of the cells themselves in terms of how they like to sprout."
Latest Headlines from Fight Aging!
Yeast is Useful in the Study of Aging, But Has its Limits - Monday, December 15, 2014
Much insight into the mechanisms of aging and metabolism in mammals has been obtained from studies of yeast, which might seem a little odd at first glance.
Nonetheless many aspects of aging and variations in response to circumstances such as calorie restriction are fairly universal and certainly very ancient from an evolutionary perspective. They are shared across a broad range of species, and thus it can be cost-effective to run rapid studies in very short-lived species that are very unlike us.
There are nonetheless important differences between these species and limits to what can be learned, however, and the research community is probably approaching these limits.
This is a very readable open access paper on the subject of whether or not yeast studies in aging are past their time, but note that the full paper is in PDF format only.
Periodontitis and Amyloid-?, Another Good Reason to Take Better Care of Your Teeth - Monday, December 15, 2014
Periodontitis produces chronic inflammation that is associated with a raised risk of cardiovascular disease and worse cognitive decline in aging.
At some point in the near future researchers will be able to control or eliminate the mouth bacteria that cause periodontitis, but for the moment we're all stuck with diligent maintenance as a primary strategy. Here is another good reason to keep up with that work.
Another Promising Example of Adoptive T Cell Therapy - Tuesday, December 16, 2014
Adoptive T cell therapies are one of the most promising methodologies for immunotherapy at the present time. This small trial is for pediatric cancer, and one might argue that you'd expect better results from immunotherapy in children, however.
The aged immune system is much less effective at all of its jobs. As is the case for stem cell therapies and their issues in treating the old, we can hope that the challenge of immune aging will simply be an incentive for the research community to develop means to overcome it so that cancer immunotherapies can work at peak effectiveness.
After all, cancer in children is rare in comparison to cancer in the old. The economic incentives thus steer developers to put considerable effort into enabling cancer treatments to work well for the old, given a promising line of research to work on.
On Studying the Epigenetics of Twins in Aging and Disease - Tuesday, December 16, 2014
Collections of twins are the closest that researchers can get in humans to an ideal study situation in which a large number of genetically identical individuals follow the same life courses.
Comparison studies with as many factors as possible made the same are a good way to tease out relevant details from an exceedingly complex system that is still poorly understood as a whole.
That system here is the sum total of human cell and tissue biology, and its changing operation over the course of a life span: the map of metabolism is at present really only a sketch of the outlines, and contains many large blank areas when it comes to the precise details.
An example of the use of twin studies is to identify twin pairs where one has a medical condition and the other does not (a set of "disease-discordant" twins), a situation that should make it much easier to identify important differences and thus more quickly identify the most relevant biochemical mechanisms involved in the development and progression of that medical condition.
An Interview with Bill Maris of Google Ventures - Wednesday, December 17, 2014
The latest Google Ventures annual report has a third of new investments going to the life sciences and health in the past year.
This is of interest principally in the context of Calico Labs and its focus on finding ways to treat aging. This interview provides a little more insight into motivations and goals - such as a strong focus on genetics as a path ahead, something that I think, unfortunately, is going to greatly limit the practical outcomes of these initiatives in terms of years of healthy life added.
Genetics and metabolic studies will broadly improve medicine and drive the creation of new and better tools in biotechnology, as does all new knowledge. Yet we all age in the same way and due to the same underlying processes: genetics are not a big factor in the grand scheme of things, and really only play a larger role in the end stages of aging, the faltering and failure of a very damaged biological system.
Alteration of genetic programs and the operation of our metabolism to slow aging is not easy and not the best way forward: the optimistic best near future outcome of drugs that can modestly slow aging is of next to no use to people already old.
The best way forward for treating aging is to work on SENS-like strategies of repair of the known forms of cellular and molecular damage that cause aging so as to build actual, working rejuvenation treatments that stop people from being old at all. This is a completely different strategic approach to medicine to that taken by the community focused on the overlap of genetics and aging, but one that has yet to gain the support it merits.
Mitochondrial DNA Amounts Correlate with Frailty and Mortality - Wednesday, December 17, 2014
Researchers here find an association between the amount of mitochondrial DNA (mtDNA) in tissues and the risk of frailty and mortality.
The less mitochondrial DNA you have, the worse off you are likely to be, or so it seems. It is an interesting result, though at this point we can only speculate about how this relates to the role of mitochondrial DNA damage in aging.
The many processes involved in mitochondrial dynamics are collectively exceedingly complex and the amount of mitochondrial DNA in cells has no direct relationship to its quality, yet both can impact health.
Global Life Expectancy Has Risen by Six Years Since 1990 - Thursday, December 18, 2014
Life expectancy at birth is a statistical measure, internally consistent and useful for comparisons across time. Insofar as it has a real meaning it is the average expected life span of a person born now if medical technology going forward exactly repeated past availability and cost over the life spans of people presently at the end of life.
Obviously that won't happen, but nonetheless this is still a useful way to keep track of progress. Since it is a measure from birth it is greatly influenced by childhood mortality and mortality due to infectious disease, and indeed much of the gains in life expectancy over the past two centuries have been due to reductions in causes of death while young.
That is no longer the case now in most parts of the world, however, and ongoing gains have more to do with reduction of mortality in later years.
This study confirms other work that shows the ballpark growth in life expectancy at birth is something like one year with every four calendar years. Adult life expectancy is also climbing, but more slowly - perhaps one year each decade.
This present pace will change as the research community starts to deliberately target aging for treatment, which has not previously been the case. Past gains in life expectancy at age 30 or 60 due to improvements in medicine have been somewhat incidental, side-effects rather than deliberately obtained results.
Theorizing on Interactions Between Telomeres and the DNA Damage Response in Cellular Senescence - Thursday, December 18, 2014
Cells can enter a senescent state in response to damage, ceasing to divide. This reduces the risk of cancer under most circumstances, but is also a part of the wound healing process.
This isn't all good, however. Senescent cells secrete factors that harm surrounding tissue function over the long term, and the growing numbers of these cells with age is one of the causes of age-related disease and dysfunction.
Researchers here look more deeply into how various mechanisms in a cell conspire to cause senescence. They are aiming to produce a more unified view of the varied entry points to this cell state. You should scroll down in the open access paper to the diagram near the end - this is a collection of mechanisms that really benefits from a visual explanation.
Sensory and Neuronal Influences on Fly Longevity - Friday, December 19, 2014
Life spans in short-lived animals can be made to vary far more in response to circumstances than the life spans of longer-lived animals.
In the case of calorie restriction there is an evolutionary explanation in that if periods of famine are longer in relation to length of life there is a selection pressure for the response to scarcity to induce greater longevity in individuals. There will probably be similar explanations for the many other ways in which a given approach can extend life in mice or flies or worms far more than it can in longer-lived mammals.
One of the discoveries made in studies of fly longevity is that neural sensing plays a strong role in guiding life span variations. Flies in fact have all sorts of interesting peculiarities in their linkage between metabolism and aging, such as the great importance of intestinal function to longevity, and the sensory influences discussed below, but it remains to be seen how many of these are of any real relevance to mammals.
Why do Some Muscles Show Fewer Signs of Aging? - Friday, December 19, 2014
Not all muscles in the body age equally, it seems, and those surrounding the eye are spared many of the degenerative changes that occur elsewhere.
Investigating why this is the case may help to inform other lines of research that aim to revert the characteristic age-related decline in stem cell activity, and thereby restore function to increasingly frail tissues.
At present groups working on reversal of stem cell aging are largely focused on the stem cell populations associated with muscles, such as satellite cells, as this is where many of the early relevant discoveries occurred, the tissues are easily accessible, and these cell types are fairly well understood and comparatively easy to work with.