Dear Future Centenarian,
What are you worth?
No, I don’t mean how much money do you have, or what your entire estate is worth. I mean, what are YOU worth?
Most of us get so caught up in business, family, day-to-day living that we never consider the monetary value of our lives.
That’s right. Monetary value. You probably never attached a dollar value to your life.
How would you quantify it? Earning power? The value of the chemical elements making up your body (about $160 – see http://www.datagenetics.com/blog/april12011/)
According to a recent article in Wired magazine, a body could be worth up to $45 million — Calculated by selling the bone marrow, DNA, lungs, kidneys, heart … as components.
I take a different slant on the value of my life.
It’s EVERYTHING I own plus whatever I can borrow. Over 40 years ago, I was attending a lecture from Dr. Andrew J. Galambos, when he said a person makes a poor value judgement when he or she won’t spend their last dime to save their life.
How many times did you walk by the organic section in a grocery store in order to save a few bucks? Did you ever pass on a nutritional supplement because of the cost? Or you thought a gym membership was an unaffordable “luxury?”
How about regular medical checkups? Or shying away from medical appointments to check out that nagging pain, a sore that won’t heal or any other physical or mental symptom because of the perceived expense involved?
Maybe you heard about a new therapy or product that could buy you more time, but it just cost too much.
Or how about the wellness or longevity conference you missed because you couldn’t afford it?
In a more serious case, what if you need an expensive surgery or therapy to treat a life-threatening disease or condition that you decide against because it would wipe you out financially?
These are all poor value judgements that could eliminate you from the gene pool.
Time to reassess?
Help the SENS MitoMouse Rejuvenation Research Project Hit Its Crowdfunding Stretch Goals
The latest crowdfunded research project undertaken by the SENS Research Foundation involves using the genetically engineered maximally modifiable mouse lineage in order to demonstrate the ability to copy a version of the ATP8 mitochondrial gene into the cell nucleus, a process known as allotopic expression, and thus prevent mutational damage to this gene from degrading mitochondrial function.
This is a modest step on the road towards bringing this class of genetic engineering project to the point of readiness for commercial development, when a biotech startup company could be created to carry it forward.
In just a few weeks of crowdfunding, the project has already hit the initial funding goal of 50,000. There are still stretch goals to reach, however – so if you want to see more work on preventing the mitochondrial contribution to aging, then join in and help.
Aubrey de Grey on the TAME Metformin Trial
As you may or may not have heard, the TAME metformin trial recently received the remaining 40 million in philanthropic funding that is needed to progress. The trial will cost 75 million in total, and to my eyes this is quite the waste of funding.
Aubrey de Grey of the SENS Research Foundation is far more polite on this topic in today’s editorial, which isn’t too surprising given our respective views on regulation.
I’ll set aside for the moment the point that metformin is a weak treatment with a small effect size on life span, unreliable animal data, life span data in humans arising from a single trial for diabetics rather than healthy individuals, and side effects that are significant in comparison to the small effect size.
A Mouse Lineage with Very Long Telomeres Exhibits Longer Life Span
Researchers here report on the generation of a mouse lineage with much longer telomeres than is normally the case. Telomeres are the caps of repeated DNA sequences at the ends of chromosomes; a little is lost with each cell division, and cells self-destruct or become senescent when telomeres become too short.
This acts as a limit on the ability to replicate for most cells in the body. Stem cells use telomerase to maintain long telomeres, however, allowing them an indefinite number of cell divisions, used to deliver daughter somatic cells with long telomeres into tissues.
Thus average telomere length in a tissue is some function of the pace of cell division and the pace at which stem cells generate replacement cells.
Depletion of Microglia Greatly Reduces Tau Pathology in Mouse Models of Alzheimer’s Disease
Today’s research adds to the body of work supporting a vital role for microglia in the progression of Alzheimer’s disease from early stages characterized by amyloid-? aggregation and mild cognitive impairment to later stages characterized by tau aggregation and severe neurodegeneration.
Microglia are one of the classes of supporting immune cell in the brain. They are similar to macrophages of the innate immune system that are present in the rest of the body, outside the central nervous system, but microglia undertake a much more varied set of tasks beyond clearing up debris, hunting pathogens, and the usual portfolio of immune cell activities.
The Resurrection of Aducanumab Doesn’t Change the Picture for Amyloid-? Clearance in Alzheimer’s Disease
It took a long time and many failed attempts for the research community to get to the point at which amyloid-? could be successfully cleared from the brains of Alzheimer’s patients.
Unfortunately, the data to date strongly suggests that this isn’t an effective approach to therapy, at least not on its own, even though it is clearly the case that the increased levels of amyloid-? in the aging brain should be removed. It is a characteristic difference between old brain tissue and young brain tissue, and there is plenty of evidence for it to be harmful.
This failure to achieve clinical success may be because amyloid-? aggregation ceases to be an important factor in later stage disease, once tau aggregation and neuroinflammation are firmly established.
The Role of Adipogenic Progenitor Cells in Muscle Stem Cell Aging
The stem cells responsible for maintaining muscle tissue decline in function with age, becoming ever less active.
This loss of function contributes to sarcopenia, the characteristic decline in muscle mass and strength that takes place with advancing age. Researchers here report on investigations of the role of adipogenic progenitor cells in the decline of muscle stem cell function.
These progenitor cells are a necessary part of the muscle stem cell niche, but their behavior changes for the worse with advancing age, disrupting the balance of intracellular signaling needed for stem cell function.
TET2 Regulates the Neuroinflammatory Response in Microglia
TET2 upregulation has been shown to improve neurogenesis and cognitive function in old mice. So it is interesting that researchers here link increased expression of TET2 with the inflammatory response of microglia in the brain.
The broader context is that is becoming increasingly clear that dysfunctional and inflammatory microglia contribute significantly to the progression of neurodegenerative conditions. This is one of many examples of apparently contradictory results to illustrate the point that cellular biochemistry is very complex. Contradictions usually indicate that there is much left to be understood about the way in which the systems studied fit together in practice.
Cardiac Glycosides, a Category that Includes Several Approved Drugs, are Found to be Senolytic
Researchers here report on the discovery that the class of drugs known as cardiac glycosides are senolytic, capable of selectively destroying the lingering senescent cells that contribute to aging and age-related disease.
These cardiac glycosides are not a good candidate for use by the self-experimentation community, however, despite the existence of low-cost generic drugs in this category. They are unpleasant compounds, quite toxic, and when used in medicine come attached to a long list of side effects that sound well worth avoiding.
It may nonetheless be the case that new senolytic drugs will be developed from these starting points, given the present enthusiasm for this line of work, by building upon the mechanisms to find less toxic small molecules that have the desired interactions with cellular biochemistry.
Treating Periodontitis Reduces Inflammatory Markers and Blood Pressure in Hypertensive Patients
Researchers here provide evidence for periodontitis, gum disease, to contribute to hypertension, chronic raised blood pressure, via inflammatory mechanisms.
Aggressively treating the periodontitis in hypertensive patients reduces both blood pressure and inflammatory markers. Periodontitis has previously been linked with a modestly increased risk of dementia, as well as increased cardiovascular mortality risk. In both cases, increased inflammation is strongly suspected to be the linking mechanism.
Processing Epidemiological Data to Show that Obesity and High Blood Pressure Cause Shorter Life Spans
Researchers here demonstrate an approach that can be used with large human epidemiological databases to demonstrate that, as expected, both greater amounts of visceral fat tissue and raised blood pressure cause reductions in life span.
The underlying mechanisms have been explored at length by the research community. Visceral fat tissue produces chronic inflammation through a variety of mechanisms, including a raised burden of cellular senescence, while raised blood pressure produces damage to fragile tissues in the brain, kidney, and other organs, and accelerates the progression of atherosclerosis.
REST Regulates Neural Activity and Influences Life Span
Researchers here report their findings on the activity of the REST gene, which both regulates neural activity and appears to influence life span, likely through indirect effects on the well-studied processes of insulin signaling.
As such, this is interesting for the connection to neural activity, but otherwise irrelevant to the future of developing means to lengthen human life span. Effect sizes related to insulin signaling are much larger in short-lived lower species than they are in long-lived higher species, and they are in any case only a way to modestly slow aging, not a road to rejuvenation.
Libella Gene Thereapeutics Moving Ahead with a Small Phase 1 Trial of Telomerase Gene Therapy
Libella Gene Therapeutics is developing telomerase gene therapy as a clinical treatment, work that results from more than a decade of studies in mice that show extended life, reduced cancer risk, and improved health.
Telomerase acts to lengthen telomeres, the repeated DNA sequences at the ends of chromosomes that shorten with each cell division. Average telomere length in the somatic cells making up any given tissue is a function of the rate of cell division versus the pace at which stem cells produce new daughter somatic cells with long telomeres. Since stem cell activity declines with age, it is no surprise to see telomere length shorten.
Significant Differences in Memory Formation are Observed in Young Mice versus Old Mice
The brain is exceptionally complex, and thus the ways in which it changes in response to the damage and dysfunction of aging are also exceptionally complex. Memory is no exception, as illustrated here.
This is one of the many reasons why the best hope for extending healthy life span significantly in the near future is to reverse the underlying damage, a comparatively simple set of processes, though not without its challenges.
Deoxydihydroceramide is Required for Much of the Cell Death Following Hypoxia
Researchers here provide evidence to show that a single type of ceramide, deoxydihydroceramide, is responsible for the tissue death following deprivation of oxygen, hypoxia, such as occurs after a heart attack.
Suppressing levels of this ceramide rapidly enough in response to the event can reduce the damage. This is one of a number of lines of research focused on attempting to preserve cells following transient hypoxia by sabotaging the mechanisms that lead to cell death.
Investigating the Mechanisms by which Klotho Increases Autophagy
Expression of the klotho gene declines with age, while approaches that increase levels of the klotho protein have been demonstrated to slow aging in mice.
Some fraction of this outcome stems from increased activity of the cellular housekeeping processes of autophagy, responsible for recycling metabolic waste and damaged molecular machinery and cellular components. Many of the methods of modestly slowing aging in laboratory species are characterized by upregulated autophagy, and some, such as calorie restriction, require functional autophagy in order to slow aging.