Healthy Life Extension
A Longevitizing Weekend
Dear Future Centenarian,Â
It™s been so long since I left town that I almost forgot what a road trip was like.
Actually, it was only a few hours, but this kind of trip was long overdue. And it was sooo worth it.
I was part of a group of close to 100 life extension enthusiasts. They included lay persons like myself. But the core were serious researchers and activists.
I go to events mainly to see old friends and to meet new ones. It fascinating to see how the ranks of serious life extensionists are swelling. And there were so many new young faces. Yeah, yeah, I know what you™re thinking. They™re just young compared to me, right? Well that too. But when I started my activities in the aging arena, most of my associates were middle aged and up. Now there are people in their 20s¦ and even teenagers.
The presentations and lectures are usually the least interesting to ADHD me. I either knew much of what was being presented, it was too far over my head to grasp or it was simply too dry. But much of this was different. There was new stuff. And exciting breakthrough stuff. Lots of interesting info on cryonics advancements. And the best was confidential. I wish I could spill the beans.
Anyway, I just wanted to share my joy with you. I shared it with Kat Cotter on the way home. We had some lively discussions in the car. One centered around the prospect of being revived in the future after being cryonically suspended (a possibility that is even more real to me now than before I saw one major new development).
Wouldn™t it be cool to wake up to suddenly witness fifty years of progress? How mind blowing would that be? And it wouldn™t be like going to sleep in 1963 and waking up in 2013. Not at all.
Because of how quickly everything is advancing, it would be more like going to sleep in 1463 and waking up today. That™s because progress is accelerating so rapidly.
But wouldn™t it be better to see things change day by day? That™s our mission. To keep aging from killing you in the first place. Cryonics is a critical, but only a backup, plan.
Latest Headlines from Fight Aging!
Making Old Stem Cells Functionally Young, Part II - Monday, October 21, 2013
Last year researchers uncovered one of the controlling portions of the process by which the hematopoietic stem cells (HSCs) that form blood decline with age. This is a part of the age-related decline of all stem cell types: researchers who subscribe to a programmed view of aging see this a part of the program of aging, a primary cause of frailty and degeneration.
Researchers who theorize that aging is a non-programmed accumulation of damage, the more mainstream view at this time, see the decline of stem cell capacity as an evolved response to rising levels of cellular and molecular damage, one that evolved in order to reduce the risk of cancer arising from the actions of damaged cells.
This difference of interpretation is important. In programmed aging world, the right thing to do given the discovery of such a mechanism is to build a therapy to adjust the levels of critical controlling proteins in order to restore a youthful mode of operation - and this is all you have to do in order to halt this part of degenerative aging. In aging-as-damage world, trying to make this change happen is a largely futile endeavor, and certainly not what should be the primary focus of the research community.
Such a therapy may produce short-term benefits, as it will temporarily minimize a secondary contribution to the frailty of aging. However, since it fails to address the underlying damage that causes aging and stem cell decline, it is like revving up a worn engine. The outcome will most likely be a greatly raised risk of cancer.
In any case, here is an update on last year's research. The scientists are making progress in following the chain of proteins involved in shutting down stem cell activity in older tissues.
Genetic Stabilization of Transthyretin, Cerebrovascular Disease, and Life Expectancy - Monday, October 21, 2013
Regular readers will no doubt recall that TTR amyloidosis, also known as senile systemic amyloidosis, is a prime suspect for the mechanism that limits human life span to the 110-120 range. Based on evidence from autopsies performed on supercentenarians, those who through luck, genes, and lifestyle manage to survive past the age of 110, these outliers are largely slain by a buildup of amyloid deposits that leads to clogging of blood vessels and ultimately to heart failure.
Transthyretin, or TTR is a protein involved in the transport of a thyroid hormone through the bloodstream. It produces amyloid when it misfolds, something that only becomes threatening in the young for the few unfortunate individuals who inherit a faulty TTR gene.
There is some research aimed at producing a therapy for this inherited form of TTR amyloidosis, and the SENS Research Foundation has funded it with an eye to also producing ways to address the age-related form. If there was a good way to periodically clear this amyloid from our tissues, that is all that would need to be done for most people in order to eliminate this very slow-moving contribution to degenerative aging.
Here is an eye-opening piece of research that shows a significant correlation between a minor variant of the TTR gene and life expectancy differences driven by cardiovascular disease and other risks. The effect is surprisingly large for a minor genetic variation, from what I recall of similar research in recent years, and I'd certainly want to see this result replicated before taking it as read. It is still a good argument for bumping up the priority for research into amyloid clearance therapies, though one could argue that perhaps other mechanisms are also at work here, since levels of thyroid hormones seem to be important in longevity.
An Update on Using DNA Methylation to Measure Age - Tuesday, October 22, 2013
The search for ways to measure both chronological and biological age from tissue samples is producing interesting early results. Chronological age is how old you are by the clock, but biological age is a measure of how rapidly the processes of degenerative aging are progressing in your case: different people slide down the slippery slope at somewhat different rates, whether because of genes, luck, or lifestyle choices.
DNA methylation is one line of research: it occurs across the whole genome and changes with age as metabolism reacts to rising levels of cellular damage. Combining measurements of the methylation of many different genes seems to produce fairly good results when it comes to identifying the age of individuals and tissues.
Mixed Results When Infusing Young Immune Cells Into an Old Mouse - Tuesday, October 22, 2013
The immune system declines with age, its army of cells capable of meeting new threats diminishing in number and capacity.
One possible form of palliative therapy for immune system aging, intended to produce benefits to the condition of the patient without addressing the underlying causes of this degeneration, is to create large numbers of new immune cells and infuse them into the patient. It is well within the present capabilities of the stem cell research community to grow new immune cells from a patient's stem cells - and indeed this has been accomplished for some years in various forms of clinical trial.
Here is a study that tries this sort of approach in mice, but with mixed results: no harm is done, and it looks like the therapy is having the intended effect under the hood, but equally the most obvious measure of whether it's doing any good in terms of boosted immune response isn't reliably improved either. More work is needed here.
Towards Reversal of Vascular Calcification - Wednesday, October 23, 2013
Calcification appears to be one of the causes of increasing vascular stiffness with age, a form of functional deterioration in blood vessels that contributes to numerous age-related conditions. Here, researchers investigate means to remove this calcium.
Transdifferentiation of Fat Cells Into Liver Cells and a Demonstration of Partial Liver Regeneration - Wednesday, October 23, 2013
This is the age of discovery for cellular control: cells are just complex machines, and with the right environment and chemical instructions the behavior and even type of a cell lineage can be radically changed.
A lot of time and funding presently goes into discovering how to achieve these goals, as greater control over cells opens up many new vistas in medicine. At present, and in parallel to research into induced pluripotency as a path to generating any type of cell from easily obtained patient samples, such as skin or fat tissue, scientists are exploring the possibilities of transdifferentiation.
At least some types of cell can be coerced into directly becoming other types of cell, without having to pass through an embryonic-like pluripotent stage, and researchers are becoming better at making this happen.
Insulin-Like Signaling and Longevity in Flies - Thursday, October 24, 2013
Insulin-like signaling is one of the better studied portions of the overlap between metabolism and aging, but even this alone is an enormously complex system. There is much left to discover.
Evolutionarily conserved insulin/insulin-like growth factor signaling (IIS) pathway governs growth and development, metabolism, reproduction, stress response, and longevity. In Drosophila, eight insulin-like peptides (DILPs) and one insulin receptor (DInR) are found, ended by dilp genes. Temporal, spatial, and nutrient regulation of DIPLS provides potential mechanisms in modulating IIS. Compensatory transcriptional regulatory mechanisms and functional redundancy that exist among DILPs make it difficult to dissect out their individual roles.
While the brain secretes DILP2, 3, and 5, fat body produces DILP6. Identification of factors that influence dilp expression and DILP secretion has provided insight into the intricate regulatory mechanisms underlying transcriptional regulation of those genes and the activity of each peptide. Studies involving loss-of-function dilp mutations have defined the roles of DILP2 and DILP6 in carbohydrate and lipid metabolism, respectively. While DILP3 has been implicated to modulate lipid metabolism, a metabolic role for DILP5 is yet to be determined.
Loss of dilp2 or adult fat body specific expression of dilp6 has been shown to extend lifespan, establishing their roles in longevity regulation. The exact role of DILP3 in aging awaits further clarification. While DILP5 has been shown associated with dietary restriction (DR)-mediated lifespan extension, contradictory evidence that precludes a direct involvement of DILP5 in DR exists. This review highlights recent findings on the importance of conserved DILPs in metabolic homeostasis, DR, and aging, providing strong evidence for the use of DILPs in modeling metabolic disorders such as diabetes and hyperinsulinemia in the fly that could further our understanding of the underlying processes and identify therapeutic strategies to treat them.
ANMT-1 and Nematode Longevity - Thursday, October 24, 2013
Sirtuin research continues despite disappointing results in mammals, and here leads to a new piece in the puzzle of linked protein mechanisms, and a novel way to extend life in nematode worms.
Using Yeast to Search for Drugs to Target Alpha-Synuclein in Parkinson's Disease - Friday, October 25, 2013
Misfolded forms of alpha-synuclein have been identified as a proximate cause of dying brain cells in Parkinson's disease (PD), and so there is considerable interest in ways to remove this protein or block its mode of action.
The research reported here is a good example of the platforms that researchers build in order to search for compounds that might be developed into drugs for this sort of task. Even when a specific protein or mechanism has been identified, at the present time it isn't yet possible to step directly to the answer and design the right molecule for the job. It remains more efficient to explore tens of thousands of candidates in the lab.
Considering Epigenetic Drift in Aging - Friday, October 25, 2013
Epigenetics is the study of mechanisms that cause changes in gene expression. Genes encode proteins, and gene expression is the complex multi-step process by which proteins are built from that blueprint.
Changes in the amount of any specific protein in circulation or in a specific location in a cell can result in significant changes in the operation of metabolism, altering the operation of cellular machinery that in turn feeds back to further change gene expression. Our biology is a massively complex web of feedback loops and linkages between genes and proteins.
DNA methylation is of the mechanisms by which gene expression is altered. It involves the addition of a chemical tag to a gene. The pattern of DNA methylation changes with aging, a process sometimes called epigenetic drift, and some of those changes are characteristic enough to be used as a measure of age.
Read More https://www.fightaging.org/archives/2013/10/considering-epigenetic-drift-in-aging.php
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"