Dear Future Centenarian,

You might have noticed, I took the holidays off and skipped two newsletters for the first time in my life. It wasn’t planned.

I was very sick (not COVID), unable to work and spent almost 100% of the entire time in bed. I will be fighting this for a while and will discuss it in detail in a future issue… because it could be important to your health.

I would like to emphasize the importance of a support group when you are going through a crisis, health or otherwise. I was near the bottom and could not have gotten through it without very special people in my life. The outpouring of love and support overwhelmed me.

It reinforced my appreciation and value of relationships.

I tend to become an island when faced with a health issue. I guess it’s the “rugged individualism” that infected me somewhere early in life. But no more. Now, I’m not only not afraid to ask for help… but I’m sure it will be the first thing I’ll do moving forward.

My good friend Joe Polish just happened to send an essay yesterday about this very topic. I have reprinted most of it below:

When people’s lives and relationships aren’t working, they need to connect with something.

Some people do this through a higher power.

Other people do it through their children.

Some people do it by being in nature.

Others do it through some sort of physical activity or nutrition.

The point is: Don’t worry alone.

I first heard this concept from my friend and Best-Selling Author Dr. Edward Hallowell.

When someone is in a hopeless state or in a dark place, they are fighting a silent battle.

Fighting silent battles are the hardest battles to fight.

Some of the richest, most famous, most powerful people on the planet – people others are often envious of – still have fears about asking for help (or they somehow feel they can’t ask for help).

If you’re fighting a silent battle, you have to find someone else you can connect with.

Before I send details in a forthcoming newsletter, I want you to know that you have an amazing health and longevity support system in the Coalition for Radical Life Extension. Don’t be afraid to use it.

Please don’t ask me anything about the issue I am facing. You will learn more in due course.

More Life,
David Kekich



Weekly News

The Harm Caused to the Hematopoietic System by Chronic Inflammation

Hematopoiesis is the generation of blood and immune cells that takes place in the bone marrow, conducted by an array of stem cell and progenitor cell populations that are differentiated from hematopoietic stem cells, a tree of subpopulations with differing tasks that together contribute to the overall outcome.

Nothing in biology is simple, and hematopoiesis is a complex, dynamic process governed by many interacting regulatory mechanisms. Hematopoietic cells respond to signals from other tissues, and particularly to the activities of the immune system, such as the inflammatory signals that arise when immune activity is needed.

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Cancer Survivors Exhibit Greater Risk of New Cancers and Higher Mortality Due to those Cancers

Today’s research materials discuss an interesting aspect of cancer epidemiology. Cancer survivors exhibit a greater risk of developing later primary cancers, unconnected to the prior cancer, and in addition suffer a greater mortality than first time cancer patients with those same cancer types.

There are a number of possible explanations for this data, two of which are noted below. The data leans strongly towards the first of the two.

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The Health Improving Effects of Aspirin Depend on Autophagy

Many groups are attempting to develop calorie restriction mimetic drugs that produce benefits to health – and slow the progression of aging – by triggering some fraction of the stress response mechanisms engaged by the practice of calorie restriction.

The most notable such mechanism is autophagy, a collection of cellular housekeeping processes that recycle damaged proteins and structures in the cell. Greater efficiency or activation of autophagy is a feature of a great many interventions known to slow aging in laboratory species.

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A Look Back at 2020: Progress Towards the Treatment of Aging as a Medical Condition

While I suspect that COVID-19 will feature prominently in most retrospectives on 2020, I’ll say only a little on it. The data on mortality by year end, if taken at face value, continues to suggest that the outcome will fall at the higher end of the early estimates of a pandemic three to six times worse than a bad influenza year, ten times worse than a normal influenza year.

The people who die are near entirely the old, the co-morbid, and the immunocompromised. They die because they are suffering the damage and dysfunction of aging. Yet the societal conversation and the actions of policy makers ignore this.

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Mitochondrial DNA in Extracellular Vesicles Declines with Age

A sizable fraction of cell signaling is conveyed via extracellular vesicles, tiny membrane-wrapped packages of molecules. Here researchers note that mitochondrial DNA is found inside extracellular vesicles, and that the amount declines with age.

Other researchers have determined that entire mitochondria are exported and taken up by cells, so one has to carefully read the methods used in papers like this to ensure that researchers are in fact looking at the smaller extracellular vesicles only.

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A Close Link Between Cellular Senescence and Idiopathic Pulmonary Fibrosis

Evidence has accumulated in recent years for the accumulation of senescent cells in aged tissues to be an important driver of fibrosis, particularly the evidence resulting from studies that employed senolytic therapies to selectively destroy sensescent cells and thereby reverse fibrosis.

Fibrosis is a malfunction of tissue maintenance, in which cells deposit excessive collagen to form scar-like structures that disrupt organ function.

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Towards Exosome Therapy for Neurodegenerative Conditions

Many approaches to stem cell therapy might be replaced in the years ahead by delivery of exosomes secreted by those stem cells.

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The Bone Marrow Microenvironment is Sensitive to the Stresses of Aging

The open access paper here is a good companion to yesterday’s review of what is known of the way in which chronic inflammation disrupts hematopoiesis. Hematopoiesis is the complex process by which hematopoietic stem cells in the bone marrow produce blood and immune cells, vital to the function of the immune system.

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Loss of LINE-1 Methylation in Cell Free DNA as a Biomarker of Aging

In recent years, transposable element activation has come to be seen as potentially important in aging. Transposable elements such as retrotransposons are DNA sequences that can copy themselves into other locations in the genome, potentially causing all sorts of disruption.

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Changing Blood Factors in Aging

Cell signaling is carried far and wide in the body via the bloodstream. The molecules involve change significantly with age, including a rise in inflammatory signaling and consequent chronic inflammation.

This is a reaction to, or consequence of, forms of damage involved in aging, but it is also a source of significant further dysfunction. That much is demonstrated by plasma dilution studies, in which improved tissue function in several organs is noted as a result of diluting the signals carried by the bloodstream in an aged body.

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Early Days Yet in the Study of Extracellular Vesicle Signaling and Exercise

Cell signaling is vital to the metabolic and health benefits of exercise.

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Targeting Apoptotic Signaling versus Targeting Mitochondrial Abnormalities to Destroy Senescent Cells

This review paper contrasts two classes of approach to senolytic therapies that selectively target senescent cells for destruction.

Inducing apoptosis in senescent cells by disrupting the balance between pro-apoptotic and anti-apoptotic signaling should be familiar to this audience, as it is the basis of some of the first senolytic drugs discovered, such as navitoclax.
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Complicating the Observations on Elite Athlete Life Expectancy

Some might hope that analysis of mortality data for elite athletes, largely meaning those who compete in professional events, could support an unambiguous relationship between physical fitness and longevity, and encourage more of us to be more active.

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Light Controlled Production of Metabolites to Better Understand the Role of Gut Microbes in Health

The activities of the gut microbiome are clearly influential on long-term health and aging, and evidence suggests that this is perhaps a similarly sized effect to that of exercise.

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Old Hematopoietic Stem Cells Transplanted into Young Bone Marrow Do Not Regain Function

Epigenetic modifications to DNA, gene expression, and cell function all change for the worse in stem cells in old tissues.

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