Dear Future Centenarian,

Last week, we covered the steps you can take today that can at least partially rejuvenate you now. The older you are, the more important it is to strengthen your immune system.

The best way to strengthen it is to address aging. However, even before we can access aggressive age-reversing technologies, we have ways to boost immune function, even though it deteriorates steadily with age.

We are les successful in fighting infections as we age. That’s why COVID-19 is so deadly to the aging population.

And that’s why I listed ways to ways to fight infections in aging immune systems in an informal report. I have attached a draft that is important for you to use to guide you through these perilous times.

Since our lives become more susceptible to infections and cancer with each passing year, the information in this letter could build your resistance to these and more.

A Wired Magazine article contributed to what follows.

To slow the coronavirus death toll we may need to slow down aging

In Europe, 95 per cent of those killed by the disease were aged 60 or over. According to the UN, the fatality rate for those over 80 is five times the global average.

Harvard biochemist Vadim Gladyshev, one of the world’s leading experts on the causes of aging – could not help but ponder if academics and pharmaceutical companies across the world were heading down the wrong path. “If Covid-19 has the greatest impact on the elderly, rather than targeting the virus, should we not be focusing more on strengthening the host?” he says.

Gladyshev’s idea was simple. Could prescribing metformin and rapamycin to the elderly as preventative measures give the most vulnerable a better chance of fighting off Covid-19, and prevent them getting to that stage?

We typically measure age chronologically based on the number of years a person has been alive, but there is a school of thought that biological age – determined by biomarkers varying from DNA expression to the length of telomeres, the tips of chromosomes – can vary depending on factors ranging from lifestyle to genetics.

Nir Barzilai, founder of the Institute of Aging Research at the Albert Einstein College of Medicine in New York, argues that the reason some people are less prone to age-related diseases such as cardiovascular disease, dementia, cancer and infections, is because their biological age is much younger. First and foremost, taking steps to lower your biological age is critical.

“By the age of 65, half of people in Europe have two diseases or more, but half have less,” says Barzilai. “For me, this is due to their differing biological ages.”

Most of the evidence that drugs might be able to reverse some of the hallmarks of aging, and thus make an elderly person more resilient to viral infections, comes from studies either in human cells or rodents.

Studies from molecular biologists across the US which used computer models to predict which drugs performed best when it came to helping the body remove the virus. Rapamycin and metformin ranked tops.

Rapamycin has been shown to enhance the effectiveness of the influenza vaccine. To make initial vaccines more effective in the elderly, their designs need to be designed to correct immune deficiencies. Barzilai says. “Rapamycin could make a difference.”

Last week, I attached PDF files for my first two of seven e-book volumes, one each of the seven steps that can help you take some control of your aging process.

As a token of my gratitude for the time you spend on reading my newsletters, I am making the first three volumes of my Maximum Longevity series free for the next three days on the kindle store.

If you don’t have a kindle, don’t worry. You can download the PDFs right here:

Click on each of the three volumes at https://www.amazon.com/s?k=kekich&i=stripbooks&ref=nb_sb_noss_2, and please give them excellent reviews at the bottom left of each book’s page.

Thank You

More Life,
David Kekich

d7d2d43a2c5a494eae8587476e739abff79fa41e847447e98867cda9d5fb566b02048748677348adb8c3dfc285546915

________________________

Weekly News

What the Exponential Rise in Mortality with Age Tells Us About the Nature of Aging

When charting rising mortality against increasing chronological age, the result is a smooth exponential curve – the Gompertz-Makeham law of mortality.

We might well ask how the exceptionally complicated process of degenerative aging, consisting of many distinct mechanisms butting heads and breaking things in a stochastic manner, can produce this outcome.

Read More https://www.fightaging.org/archives/2021/03/what-the-exponential-rise-in-mortality-with-age-tells-us-about-the-nature-of-aging/

Insight into the Dysregulation of Myelin Maintenance in the Aging Brain

Today’s research materials report on an investigation of the age-related loss of myelin in the nervous system. The insulating sheath that surrounds nerves is made up of myelin.

Its presence ensures the proper conduction of nerve impulses along the axons that connect neurons in the nervous system. The structure and maintenance of myelin sheathing has been most studied in the context of demyelinating conditions such as multiple sclerosis, in which the immune system causes a breakdown of myelin.

This leads to increasingly severe symptoms as the nervous system loses its ability to function.

Read More https://www.fightaging.org/archives/2021/03/insight-into-the-dysregulation-of-myelin-maintenance-in-the-aging-brain/

A Discussion of Systemic Inflammation and its Contribution to Dementia

A growing faction within the research community has come to view chronic inflammation as one of the most important mechanisms that contribute to degenerative aging. It is certainly the case that in the Alzheimer’s field the evidence of recent years points toward inflammation as the major mediating mechanism linking the diverse pathologies of this neurodegenerative condition.

In today’s open access paper, researchers put forward their view of the connections between inflammatory disease outside the brain and inflammatory disease inside the brain. They contribute to one another, creating an accelerating downward spiral of damage and dysfunction.

Read More https://www.fightaging.org/archives/2021/03/a-discussion-of-systemic-inflammation-and-its-contribution-to-dementia/

Fisetin Reduces D-Galactose Induced Cognitive Loss in Mice

D-galactose is often used by researchers in order to induce aging-like symptoms in mice. It is a damaging compound, provoking oxidative stress, inflammation, and cellular senescence.

That in turn produces loss of tissue and organ function in ways that can appear similar to the outcomes of degenerative aging. In today’s open access paper, researchers show that injection of fisetin can significantly reduce the harmful outcomes produced by D-galactose, including the loss of cognitive function.

Read More https://www.fightaging.org/archives/2021/03/fisetin-reduces-d-galactose-induced-cognitive-loss-in-mice/

Reprogramming Cancer Cells into Normal Somatic Cells

Cell reprogramming involves changing the expression of top-level regulatory genes, picking targets that will radically change cell form and function.

Given a suitable recipe, many of which have been established, forms of cell reprogramming can be used to change somatic cells into stem cells, or change somatic cells of one type into somatic cells of another type. In the other direction, numerous approaches can be used to guide stem cells into differentiating into varieties of somatic cell.

Read More https://www.fightaging.org/archives/2021/03/reprogramming-cancer-cells-into-normal-somatic-cells/

Considering Longevity Medicine and the Education of Physicians

A part of the process of moving therapies to slow or reverse aging from the laboratory to the clinic is educating the physician population. While the scientific community is largely on board with the goal of controlling the processes of aging, the same is not true of the medical community.

The first useful rejuvenation therapies already exist, in the form of senolytic treatments, particularly the combination of dasatinib and quercetin. There is thus more advocacy and persuasion yet to be accomplished in order for physician networks to emerge and enable widespread use of the first viable treatments for aging.

Read More https://www.fightaging.org/archives/2021/03/considering-longevity-medicine-and-the-education-of-physicians/

Researchers Generate Thyroid Organoids Capable of Restoring Function in Mice

When building functional organ tissue from the starting point of pluripotent stem cells, a different recipe is required for each different tissue type. Good progress is being made in establishing these recipes, and over the past decade the research community has steadily expanded the number of organs for which tissue engineered organoids can be constructed.

Read More https://www.fightaging.org/archives/2021/03/researchers-generate-thyroid-organoids-capable-of-restoring-function-in-mice/

In Search of Transcriptional Signatures of Aging

For some years the ability to gather biological data has far outpaced the ability to analyze that data usefully. The genome, the epigenome, the proteome, the transcriptome, and more, all repeated over countless thousands of animals and humans.

Enormous vaults of data now exist in all branches of the life sciences, enough to keep researchers occupied for decades. In order to speed up the process of analysis and understanding, scientists are increasingly applying modern tools of machine learning to life science data.

Read More https://www.fightaging.org/archives/2021/03/in-search-of-transcriptional-signatures-of-aging/

A Pace of Aging Biomarker Correlates with Manifestations of Aging

Researchers here note the results from a study in which a comparatively simple compound biomarker of aging exhibited correlations with the manifestations of aging and age-related disease. The past decade of work on measurement of aging has shown that it is comparatively straightforward to produce metrics that reflect the increasing burden of damage and dysfunction.

Making use of the best of these metrics to assess potential approaches to the development of age-slowing and rejuvenating therapies has yet to be carried out in any widespread fashion, however.

Read More https://www.fightaging.org/archives/2021/03/a-pace-of-aging-biomarker-correlates-with-manifestations-of-aging/

Targeting Tissues with Extracellular Vesicles

Much of cellular communication takes the form of secretion and uptake of extracellular vesicles, tiny membrane-wrapped packages of molecules.

The use of these vesicles as a basis for therapy is spreading. Since first generation stem cell therapies appear to produce their benefits via the signals generated by transplanted stem cells, why not use vesicles harvested from stem cells instead the cells themselves?

The logistics are far less challenging, the costs lower. Further, vesicles can be engineered to contain novel contents, or given different surface features.

Read More https://www.fightaging.org/archives/2021/03/targeting-tissues-with-extracellular-vesicles/

Calorie Restriction Slows Aging of the Gut Microbiome in Mice

The gut microbiome is known to change in harmful ways with advancing age. In old people there are too many inflammatory microbes, versus too few microbes generating beneficial metabolites.

Researchers here note that the practice of calorie restriction, well established to slow aging and extend life in numerous species, prevents much of this age-related shift in microbial populations in mice.

Read More https://www.fightaging.org/archives/2021/03/calorie-restriction-slows-aging-of-the-gut-microbiome-in-mice/

Mitochondrial DNA Heteroplasmy in the Aging Heart

Every cell contains hundreds of mitochondria, bacteria-like structures that carry their own small genome, the mitochondrial DNA. Mitochondria replicate like bacteria to maintain their population size, and are destroyed when worn and damaged by the quality control mechanism of mitophagy.

The primary task undertaken by mitochondria is the generation of chemical energy store molecules (adenosine triphosphate, ATP) to power the cell, but they also play many other roles in fundamental cell processes.

Mitochondrial DNA is poorly protected and repaired in comparison to nuclear DNA, and accumulates mutational damage over time. It is argued that this damage contributes to loss of mitochondrial function, and thus faltering tissue function, particularly in energy-hungry organs such as the heart.

Read More https://www.fightaging.org/archives/2021/03/mitochondrial-dna-heteroplasmy-in-the-aging-heart/

Evidence for Head Injuries to Accelerate Cognitive Decline in Following Decades

Researchers here present epidemiological evidence for head injuries to leave permanent consequences that accelerate later cognitive decline.

Speculatively, the mechanisms by which this might happen could include an increased lasting presence of senescent cells in injured tissue, raising local levels of inflammation.

Certainly there is suggestive evidence for some forms of injury, including injuries to the brain, to leave a lasting mark in the form of raised inflammation in tissues. Senescent cells are frequently involved in inflammation-related mechanisms and conditions.

Read More https://www.fightaging.org/archives/2021/03/evidence-for-head-injuries-to-accelerate-cognitive-decline-in-following-decades/

Considering Rate-Limiting Processes in the Progression of Aging

In this paper, the author argues for greater emphasis to be placed on identifying rate-limiting processes in aging, here termed “flux-controlling” processes.

One can tinker with various aspects of cellular metabolism connected to any one given molecule or class of molecules, and do so in many different ways, but any given approach may or may not interact with a rate-limiting step. If it doesn’t, then the outcome will not tell us all that much about whether or not this molecule, this process, is important in aging.

Read More https://www.fightaging.org/archives/2021/03/considering-rate-limiting-processes-in-the-progression-of-aging/

The Tripartite Phenotype of Aging

Here, researchers advocate for a greater consideration of the role of random chance at the cellular level in the variations in life span exhibited by individuals of any given species.

Why do people age at different rates and why does human life span exhibit a wide range? Exploration of human genetic data increasingly suggests that very little of this variation between individuals is due to our genes.

That in turn might suggest that stochastic processes of damage and dysfunction are of greater importance to variations in aging than was previously thought to be the case by the research community.

Read More https://www.fightaging.org/archives/2021/03/the-tripartite-phenotype-of-aging/