Longevity News Digest
Happy New Year! (2 Year-Ending Gifts)
Dear Future Centenarian,Â
Here™s to an amazing 2015!
Look how we™re wrapping up the year. This breakthrough could lead to major life enhancing and life extending therapies sooner than we thought.
And I also just found out I™m a recording artist. For your listening pleasure, you can find me at the 2:02 portion of this song. O
Latest Headlines from Fight Aging!
Preliminary Evidence Suggesting Long Term Memory is Not Stored in Synapses – Monday, December 22, 2014
Long-term memory is thought to exist as structures within synapses, which is why the destruction of synapses in the earlier stages of neurodegenerative conditions such as Alzheimer’s disease causes memory loss.
If memory doesn’t exist in the synapses, however, then there is more of a possibility of restoration through effective treatments for the condition.
At this point models of long-term memory that put the data somewhere other than the synaptic connections between neurons has an uphill road to travel: past years have seen the accumulation of good evidence for synaptic memory storage, such as experiments in which memory in rats is erased and restored. Nonetheless, this is interesting work.
A Review of the Endocrinology of Aging – Monday, December 22, 2014
Here is an open access review of what is known of changes in the endocrine system that occur with aging. This is many steps removed from the low-level cellular and molecular damage that causes degenerative aging.
It is a good example of a body-wide set of linkages between organs and signals and processes in which every change or failure in one component part will cause corresponding reactions in all of the other components.
A sizable field of medicine continues to focus on these changes, trying to find ways to shift levels of hormone signals to be closer to measures taken in youth. In past decades this has produced some legitimate treatments for a variety of age-related conditions that are better than nothing, but unfortunately also a fraudulent network of false “anti-aging” claims and purported therapies that cloud the waters and make any online discussion of this topic difficult.
Where legitimate, as an approach it is acting at the wrong level, chasing after secondary and later effects in a very complex system rather than addressing the root causes of changing hormone levels. Consequently it has been challenging to produce more than marginal benefits, which is much as you’d expect if you’re trying to tinker a broken system into better performance without actually fixing the breakage.
Still, here as elsewhere, there is enormous inertia and resistance to the new concepts of addressing root causes rather than messing with metabolism in this way, and researchers continue to work on ever more sophisticated ways of trying to make the broken machinery perform.
Updates on the Biodemography of Aging and Longevity – Tuesday, December 23, 2014
This is a review of published research in the biodemography of aging produced by one particular group over the past few years. A lot of their work sits within the framework of reliability theory, which is a fairly high-level but useful model of damage and failure in complex systems. When applied to demographic data on aging reliability theory can produce some interesting predictions, notably that we are all born with an initial load of damage – we don’t start from a blank slate. This feeds into observations such as those below on statistical differences in longevity correlating with parental age.
Cellular Senescence is Complicated – Tuesday, December 23, 2014
Cellular senescence is a process that serves to reduce cancer risk by removing damaged cells from the cell cycle and irreversibly suppressing their ability to proliferate.
Unfortunately it is also one of the root causes of degenerative aging, as when present in large numbers these cells cause significant damage to surrounding tissue structure and function. They don’t go away either: by the time old age rolls around, a sizable fraction of skin cells are senescent, for example. Ideally these cells would be destroyed by the immune system, but that only happens for a fraction of them, and in any case the immune system itself progressively fails in all of its tasks due to the damage of aging.
As the tools of biotechnology rapidly become better and cheaper, researchers are discovering new complexities in every area of cellular metabolism, and senescence is no exception. Cells are exceedingly complicated machines. All of the consensus opinions on how senescence works might be thought of as high level generalities, but there are a lot of exceptions and new information.
Senescence isn’t as absolutely irreversible as thought; it plays a beneficial role in wound healing; it might steer embryonic development; there are a range of novel ways in which cells can enter a senescent state; and so forth.
Fortunately it is possible to short-cut all of this complexity and skip directly to destroying senescent cells. We know they are bad for us in volume regardless of how exactly they are coming into being, and thus the research community should aim at selective removal of these cells, producing a therapy for periodic application that is perhaps based on some of the work on targeting cell types taking place in the cancer research establishment.
Say once a decade, since we know that humans can certainly live for at least three decades without significant impact from cellular senescence. Sadly the direct approach is poorly funded in comparison to ongoing investigations of senescence in detail, but this is par for the course in everything that might actually have some meaningful impact on aging. This must change. Meanwhile here is another research paper uncovering yet more of the complexity of cellular senescence.
A Role for Hydrogen Sulfide in Calorie Restriction – Wednesday, December 24, 2014
A great deal of effort over the past fifteen years has gone into efforts to fully understand how calorie restriction works to improve health and extend life. The research community would like to have sufficient knowledge to produce drugs that mimic this effect.
At this point what researchers have is still a sketch, however: near everything in the operation of metabolism changes in response to reduced calorie intake, which has made it very challenging to figure out cause and effect.
Meanwhile, new aspects of calorie restriction biochemistry are discovered on a regular basis these days, with no signs of an end in sight. Researchers here find that one of the benefits provided by calorie restriction is not, as thought, due to increased cellular antioxidant responses, but instead involves hydrogen sulfide (H2S) in some yet to be identified way.
Hair Regrowth as a Pointer to the Role of Immune System Activity in Tissue Regeneration – Wednesday, December 24, 2014
The immune system is known to play an important role in regeneration, but the details are still being uncovered.
Nonetheless at some point in the near future manipulation of immune cells may prove to be a viable alternative path in regenerative medicine, a different way to achieve faster healing or spur tissue regrowth where it does not normally occur.
Towards a Signature of Age in Blood Plasma – Thursday, December 25, 2014
Various tools are presently under development as means to measure age from tissue samples, such as by looking at DNA methylation patterns. A marker for biological age is very much needed in order to speed up development of treatments for aging, as it is presently very expensive and time-consuming to evaluate any sort of putative longevity-enhancing therapy.
This is true even in rodents, where it can cost millions of dollars and take three to five years to run a single life span study – and the costs only grow for longer-lived mammals. If much of that could be replaced by a short test carried out immediately before and after treatment then research could proceed much more rapidly. Here is one example of work that might lead to such a marker for age.
Falling Mitochondrial DNA Copy Number in Type 2 Diabetes – Thursday, December 25, 2014
A herd of bacteria-like mitochondria exist in every cell in the body, constantly dividing, fusing, and swapping component parts among one another, as well as being destroyed when damaged by cellular quality control mechanisms.
Mitochondria are responsible for a range of tasks vital to the cell, but the best known involves the creation of ATP chemical energy stores used to power cell operations. Each mitochondrion has at least one copy of the small set of mitochondrial DNA, separate from the DNA in the cell nucleus.
As long term readers know damage to this mitochondrial DNA is implicated as one of the primary causes of degenerative aging, leading to a Rube Goldberg chain of consequences that in the end produces a small population of very dysfunctional cells that export damaging reactive molecules to harm tissues both near and far in the body.
Mitochondrial DNA doesn’t just become more damaged with age, the number of distinct mitochondrial genomes in a cell – called the copy number – falls dramatically in all cells in many tissues. This has no straightforward or well-understood relationship with mitochondrial damage: it isn’t just the dysfunctional cells that have lower copy numbers, and higher copy numbers may be a response to damaged DNA.
Falling copy number doesn’t linearly correlate with number of mitochondria or the mitochondrial output in term of necessary energy stores for cellular processes, but it does seem to have a significant impact. As an example, researchers here suggest that reduced mitochondrial copy number and its effects on function are a proximate cause for lost insulin production in type 2 diabetes.
Are Advanced Glycation End-Products Protective as Well as Harmful? – Friday, December 26, 2014
Some of the important processes in aging are known to be initially protective at lower levels and later harmful. Senescent cell accumulation is a good example, as it acts to suppress cancer incidence by permanently removing the most at risk cells from the cell cycle. Yet as senescent cells gather in numbers over the years their actions significantly degrade tissue and organ function.
In the paper quoted below researchers propose that the formation of advanced glycation end-products (AGEs) has a similar protective effect when it comes to cancer, and provide some other benefits besides. Yet their presence is definitely harmful in a number of ways when significant amounts of long-lived AGEs are present, causing chronic inflammation and degrading the mechanical properties of tissues such as skin and blood vessel walls by forming cross-links between structural proteins.
Fortunately in both of these cases periodic removal – of senescent cells or AGE cross-links – on a timescale of once every decade or so would allow us to have our cake and eat it. It would prevent pathological levels of these changes from emerging, as we know humans are quite capable of living for three decades without suffering serious consequences from aging, while still permitting lower and possibly protective levels to arise.
Mitochondrial DNA Damage in Atherosclerosis – Friday, December 26, 2014
Mitochondria, the power plants of the cell, have their own small genomes left over from their ancient origins as symbiotic bacteria. This mitochondrial DNA (mtDNA) becomes damaged in ways that evade cellular quality control mechanisms as a consequence of the normal operation of metabolism.
Over the course of a human life span this leads to a small population of cells overtaken by dysfunctional mitochondria, emitting a flood of damaging reactive molecules into surrounding tissues. This contribution to degenerative aging could be removed entirely if we had the means to regularly replace and remove these damaged mitochondrial genomes, or alternatively to deliver an ongoing supply of mitochondrial proteins – as DNA damage is only significant because it removes or alters the blueprints required to generate specific proteins.
It is the proteins that are needed for correct mitochondrial function to continue. Given a major research and development initiative working prototypes of these repair technologies are actually only a few years away, but despite a number of teams working on these approaches at a slow pace, until much more funding is devoted to this cause that few years away will continue to be the case.
Here is a recent open access review of the mechanisms by which mitochondrial DNA damage is thought to promote the development of atherosclerosis, such as – but not limited to – formation of oxidized low-density lipoprotein (LDL) molecules that aggravate cells in blood vessel walls into an ultimately harmful reaction.
They draw in immune cells that try to consume and break down the LDL, but these cells can be overwhelmed to turn into foam cells or die to create a clot of debris that can grow to become a plaque. That in turn can cause a catastrophic blockage of blood flow, and death.
DISCLAIMER:Â News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.fightaging.org/
David A. Kekich
Maximum Life Foundation
“Where Biotech, Infotech and Nanotech
Â Â Â Â Meet to Reverse Aging by 2033″