Dear Future Centenarian,
If you live in the US, you most likely celebrated Thanksgiving last Thursday.
Thanksgiving is the day we traditionally count our blessings (although ideally we would do that every day).
Giving thanks, expressing gratitude… and sharing our day with those we love most.
A tradition I have cherished most of my life.
And we life-extensionists have more to be grateful for than most. Primarily, the rapid and ever-accelarating pace of medical science and technologies.
I’m referring to those technologies that keep us biologically younger for longer… and those that hold promise to REVERSE the human aging process.
There are suddenly many researchers and companies contributing to the confluence leading to full-body rejuvenation.
Perhaps none is as promising as gene therapy.
Yes, it is expensive, just like nearly all new technologies. But as the field matures, prices tend to drop rapidly when supply and demand increase.
These pure market forces act like a magic wand, delivering benefits to millions and millions – seemingly overnight once they hit a tipping point.
Meanwhile, the wealthy globe-trotting early adopters pave the way to make it possible for the rest of us to recapture youthfulness by paying today’s prices which fund more research, thus eventually lowering the costs for all.
Over four years ago, Liz Parrish of BioViva USA stepped up as the world’s first dual gene therapy patient.
Some say she took a reckless risk. But she immersed herself in the data first and was confident it was safe. She experienced no negative outcomes.
The therapies she got target the aging process itself, but also aging related conditions and diseases such as sarcopenia (muscle wasting), atherosclerosis, even dementia and more.
Below, you will find Liz’s before and after photos.
Granted, these photos were not taken under ideal conditions. Different lighting and different backgrounds.
But knowing Liz as I do, I can attest to her looking younger than she did in 2015.
In fact, her “after” biomarkers pointed to a younger person. For example, her measured telomere length showed a remarkable 33 year age reversal during that time.
The even better news is, the technology has improved over the past four years and should continue doing so.
Technologies such as gene therapies could be what you need to bridge the gap between your biological age today and your age when full-body rejuvenation emerges.
Of course, it’s more important than ever to continue your good lifestyle habits, primarily diet and exercise.
Notes on the 1st Alcor New York Science Symposium
This past weekend, I was in New York City for a meeting organized by Alcor New York, a cryonics community group that is presently seeking to set up a more robust Biostasis Society of New York complete with well-organized standby capacity to help people achieve a successful cryopreservation at the end of life.
Setting aside technical issues, the greatest challenge in cryopreservation is the fact the euthanasia, and thus the ability to arrange time of death, remains largely illegal. Hence there must be expensive standby operations, suboptimal deaths that cause significant damage to the brain, and a scramble to ensure rapid cooldown and preservation when death does occur.
Since there are only two reputable cryonics providers in the US, local organizations capable of coordinating standby and transport are essential.
Slower DNA Damage Accumulation in Immune Cells Correlates with Species Life Span
Today's open access research is an assessment of DNA damage accumulation in a variety of species, showing the pace of mutational damage correlates with species life span, at least as assessed here in immune cells from blood samples, and using a marker that identifies the response to short telomeres as well as forms of DNA damage.
The DNA of the cell nucleus, the genetic blueprint for near all of the proteins produced in a cell, accumulates damage over time due to the normal haphazard chemical reactions that take place constantly inside cells.
These mutational changes are largely irrelevant to cellular operation, but some can cause disruption in metabolism, or, worse, make a cell cancerous, by causing certain proteins to be produced in a broken or altered state. Near all mutational damage to DNA is quickly repaired by the highly efficient array of DNA repair mechanisms that a cell is equipped with. But some inevitably slips past.
The Tight Junctions of the Blood-Brain Barrier in Aging and Neurodegeneration
Today's open access paper is a review of the tight junction structures of the blood-brain barrier in aging and neurodegeneration. The blood-brain barrier is a structure of specialized cells that lines the blood vessels that pass through central nervous system tissue.
The barrier allows only certain molecules and cells to pass between blood vessels and the central nervous system, thus preserving its separation from the rest of the body. Unfortunately the integrity of the blood-brain barrier breaks down with advancing age, and the entry of unwanted molecules and cells into the brain then contributes to inflammation and tissue dysfunction.
Werner Syndrome is Strongly Mediated by Mitochondrial Dysfunction
Researchers here report that NAD+ upregulation to improve mitochondrial function, via supplementation with nicotinamide riboside and nicotinamide mononucleotide, does a decent job of rescuing the life span of flies and worms with the genetic mutation that causes Werner syndrome.
It is not quite all the way restored to match wild-type animals, but close. Werner syndrome is a DNA repair deficiency condition in which patients exhibit, at the high level, what appears to be accelerated aging: early onset of a range of age-related conditions, early mortality.
Read More https://www.fightaging.org/archives/2019/11/werner-syndrome-is-strongly-mediated-by-mitochondrial-dysfunction/ It is not, however, accelerated aging.
Cardiac Amyloid Buildup Correlates with Risk of Atrial Fibrillation
Amyloids are misfolded proteins that become insoluble in their incorrect configuration, forming structures that encourage other molecules of the same protein to also misfold in the same way. These structures spread, grow, and clump together into solid deposits in and around cells.
Only a handful of proteins can form amyloid, and many are associated with age-related disease. Consider the amyloid-? characteristic of Alzheimer's disease, for example. The better understood forms of amyloid are known to be accompanied by a surrounding halo of toxic biochemistry that harms cells and cell function.
Setting aside genetic diseases in which proteins are created in a damaged form, more prone to amyloid formation, there are a couple of forms of amyloid that tend to show up in heart tissue with age, light chain amyloid and transthyretin amyloid.
Upregulation of Autophagy Improves Vascular Function in an Animal Model of Type 2 Diabetes
Autophagy is the name given to a collection of cellular maintenance processes that recycle damaged structures, unwanted protein, and other metabolic waste.
Many forms of stress, such as heat, lack of nutrients, and so forth spur greater autophagy, and this is thought to be a large part of why mild, temporary stress can produce lasting benefits to health - a process known as hormesis.
To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence?
Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable processes of aging that, until therapies exist to repair this damage, will cause decline in muscle tissue over time even for those who maintain their fitness as best as possible.
Researchers here consider the evidence for skeletal muscle tissue to do more than just move us around, but also to be an active participant in many aspects of metabolism. The focus in this open access paper is on the immune system: to what degree does sarcopenia contribute to the loss of immune function that also occurs with age?
In Search of Genes that Were Lost in Longer-Lived Mammals
Researchers here describe an interesting approach to improving the understanding of how differences in species longevity arise from differences in the operation of cellular metabolism.
They report on a search for genes in short-lived mammals, mice in this case, that have been lost in long-lived mammals such as our species. Finding such genes can then lead to an investigation of specific aspects of cell and tissue function relevant to life span.
As is often the case in this field, the work is of scientific interest, but not really all that relevant to near future efforts to produce rejuvenation. A complete understanding of how exactly aging progresses in detail and which mechanisms are more or less important would be helpful, but it is by no means necessary. The research and development community can forge ahead to repair the known causes of aging without a full understanding of aging - indeed, this is already progressing quite well in the matter of stem cells and senescent cells.
Topical Rapamycin Evaluated as a Treatment for Skin Aging
Given the attention that descends upon any prospect of reversing skin aging, I should probably open by saying that much of the data here for extended low dose topical treatment with rapamycin over eight months, that regarding visible skin aging and collagen production, is no more exciting than that obtained by any number of other approaches, such as topical application of keratinocyte growth factor (KGF).
Effect sizes are the only thing that matters, and also the one thing that all too many observers fail to consider. Looking at the paper, I would say that the primary point of interest is the 50% reduction in markers of cellular senescence in skin. Given what is known of rapamycin this seems unlikely to be a senolytic effect, so not destruction of existing senescent cells, but rather a reduction in the number of cells becoming senescent. This in turn suggests that there remains some meaningful level of ongoing natural clearance of lingering senescent cells at older ages.
Common Mechanisms of Blood-Brain Barrier Dysfunction to Underlie Many Forms of Damage to the Brain
Researchers here note a signature of blood-brain barrier dysfunction that is common in many forms of damage and injury to the brain, suggesting it to be more broadly relevant to pathology than suspected.
There is already good evidence for dysfunction of the blood-brain barrier to be an early feature of neurodegenerative diseases. The specialized cells of the blood-brain barrier line blood vessels that pass through the central nervous system, managing the passage of molecules and cells. When the barrier fails, unwanted molecules such as fibrogen can enter the brain to cause inflammation - and chronic inflammation in the brain is known to be important in the progression of neurodegeneration.
Nanotics Aims at Preventing Senescent Cells from Evading Immune Surveillance
Nanotics works on a nanoparticle platform that can modulate cell signaling via depletion of arbitrary target signaling molecules, something that has a great many potential uses, such as altering the behavior of the immune system.
Given the present level of interest in clearance of senescent cells as an approach to treating aging, it isn't surprising to see platform companies of this ilk turning their attention to the production of senolytic treatments in addition to their existing pipelines. Here the approach is to deny lingering senescent cells the capacity to protect themselves against immune surveillance, and thus enable the immune system to destroy a greater fraction of these errant cells than would otherwise be the case.
Towards Small Molecule Drugs that Suppress ?-Synuclein Aggregation
Researchers here report on efforts to find small molecules that can interfere in the molecular biochemistry of synucleinopathy. Parkinson's disease is the best known of the synucleinopathies; these are neurodegenerative conditions characterized by the misfolding and consequent aggregation of ?-synuclein.
This is one of a handful of proteins in the body that can misfold in a way that encourages other molecules to also misfold, forming structures and then solid deposits that cause considerable harm as they spread throughout the aging brain. The best form of therapy would be some form of periodic clearance of these errant molecules, but, absent that, a way to interfere in the processes of misfolding and aggregation would be a step forward.
SHMT2 in the Age-Related Decline of Mitochondrial Function
Mitochondria are the descendants of ancient symbiotic bacteria, several hundred of them in every cell. Their primary task is to produce the chemical energy store molecule adenosine triphosphate (ATP) to power cellular operations.
With aging, mitochondria throughout the body decline in function. They change their morphology, the balance between fission and fusion shifts, the ability of the cell to remove worn and damaged mitochondria is impaired. Researchers have made some inroads into the proximate causes of these global changes, meaning upregulation or downregulation of specific proteins, but the connection to the root causes of aging remains unclear.
The research noted here is an example of continued efforts in this direction, and in this specific case offers a hint that mitochondrial decline with aging may be a part of the evolved trade-off between (a) cancer risk due to active cells in a damaged environment and (b) functional decline due to inactive cells that fail to maintain an increasingly damaged environment.
Reporting on the Aging Research and Drug Discovery Meeting Held at BASAL Life 2019
Earlier this year the Aging Research and Drug Discovery meeting was organized as a part of the broader BASAL LIFE scientific conference. As is traditional for such events, the organizers put together a paper reviewing the proceedings. A few of the early highlights are noted below, but many more presentations are briefly discussed in the open access paper. It is a representative selection of the present distribution of projects and research goals in the scientific community focused on intervention in the aging process.
Exercise Reduces Inflammatory Leukocyte Production, Slowing Development of Atherosclerosis
Researchers here report on the investigation of a lesser known mechanism by which exercise lowers risk of cardiovascular mortality. It alters cell signaling that drives the creation of inflammatory immune cells, and in turn thus accelerates the development of atherosclerosis.
Atherosclerosis is the buildup of fatty deposits called plaques that narrow and weaken blood vessels, leading to heart attack and stroke. It is a condition resulting from dysfunction in the innate immune cells called macrophages that are responsible for clearing out fats from blood vessel walls. Once atherosclerosis has started, chronic inflammation from any source will accelerate its progression, by making it even harder for macrophages in an atherosclerotic plaque to adopt the set of behaviors required to help clear the damage.