Dear Future Centenarian,

One of the oft cited “hallmarks of aging” is cellular senescence, but not everyone is familiar with what this means. It is a state cells go into under certain conditions, commonly thought to be a defense against cancer, cells begin going into senescence under a variety of conditions believed to signal risk of tumor growth to the cell.

CLICK HERE for a test to gauge your body’s cellular senescence burden.

The trade-off is that senescent cells stop dividing, which means the body has fewer resources to maintain its systems, which in turn leads to imbalances in the body, leading to even more senescent cells. It is easy to see how this is, up to a certain point, a lifesaving function of the cell.

Your body may be deprived of resources, but so are potential tumors. Such a feature probably emerged as part of the evolutionary war between organisms and the tumors which would kill them without protocols in place to stop them.

Cellular senescence is a war of attrition and can very much be understood as a core part of aging.

Our bodies fight valiantly against the specter of cancer, but in doing so they lose a little ground, leave the battle weaker, and eventually, so many cells have been sacrificed, have become senescent, that the organism can no longer sustain itself. In other words, it dies of old age.

If we could make it so that less of our cells become senescent, or better yet, allow senescent cells to resume divisions, there might not be much of a fundamental difference between that and reversing aging, at least in part.

This is the reason why cellular senescence is considered a hallmark of aging, it is one of the factors which, if better understood, would reveal a lot about how aging works. A cure for cellular senescence might work as a complete, or at least partial cure, for aging as it is.

The perceived danger of senescent cells go beyond a simple lack of productivity, however. Cells generally reproduce, senescent cells do not, but still accumulate energy. It is believed that instead of replicating, producing offspring, these cells produce unwanted byproducts.

It is hypothesized that one such “byproduct” of senescent cells are cytokines, which encourage an overactive immune system, thereby accelerating the aging process.

However, because senescent cells play a role in preventing growth in tumors, as well as in other processes, this is not a question of simply eliminating senescence, but instead, understanding how to manage senescence in concert with other processes to extend human health span.

Because while senescent cells may play a certain role, they eventually cause others and accelerate the deaths of their hosts.

Cellular senescence, like so many other parts of biology, is intricately connected to other processes. Maintaining health in any one of the bodies various systems and micro-environments can slow the accumulation of senescent cells.

And a class of drugs and even supplements called senolytics do a good job of periodically clearing senescent cells. You can find information at https://age-reversal.net/.

A stronger and more permanent solution, maintaining or lengthening telomeres, is associated with a marked increase in life and health span. Telomerases are kinds of protective caps on the end of DNA, over time the gradual shortening of these signals to the cell that damage may be occurring, which leads to the cells becoming senescent to protect themselves.

Telomerase lengthening treatments are already provided by gene therapy. This is not the only thing which regulates cellular senescence, but certainly a contributing factor.

One of the interesting qualities of health interventions is that they can have cumulative effects, as we gain ground, it becomes easier to take, both in terms of the science and as the treatments are applied.

Someone who has had interventions of one kind is likely to see improvements in an array of areas. Telomerase lengthening is just one improvement, but that improvement leads to other improvements over time.

Genomic stability can engender molecular stability, encourage the body to generate the kinds of proteins associated with youth simply because it senses that the body is more useful.

The further upstream a solution is, the more likely it is that the rest of the body will be able to respond to that solution and that a cure will have more permanency.

And that is the quest of the century for medicine and genetics, to find a solution which not only reverses aging, but can prevent it from happening altogether, because it makes the body’s other systems fall into place.

More Life,
David Kekich

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Weekly News

The Importance of the Glymphatic System in Clearing Metabolic Waste from the Brain

Many neurodegenerative conditions are characterized by the aggregation of altered proteins, such amyloid-?, ?-synuclein, tau, and others.

Once altered they can form solid deposits with a halo of surrounding biochemistry that is toxic and disruptive to the normal function of cells in the brain. Why do these protein aggregates only become significant in later life?

Read More https://www.fightaging.org/archives/2021/02/the-importance-of-the-glymphatic-system-in-clearing-metabolic-waste-from-the-brain/

Towards Therapies Targeting the Mechanisms of Transthyretin Amyloidosis

There are twenty or so different proteins in the human body that can form amyloids, a misfolding of the protein that can encourage other molecules of the same protein to misfold in the same way.

These misfolded proteins join together to form solid deposits – amyloids – that are associated with a complex, problematic biochemistry that disrupts cell and tissue function. Once underway in earnest, this formation of amyloids and the resulting pathology is known as amyloidosis.

Read More https://www.fightaging.org/archives/2021/02/towards-therapies-targeting-the-mechanisms-of-transthyretin-amyloidosis/

Loss of Capillary Density as a Hallmark of Aging

In today’s open access paper, researchers add to the present body of evidence for loss of capillary density to be an important mechanism of aging.

All tissues are packed with capillaries, hundreds passing through every square millimeter in cross-section. This density is lost with age, and that reduces the supply of nutrients and oxygen to cells.

Read More https://www.fightaging.org/archives/2021/02/loss-of-capillary-density-as-a-hallmark-of-aging/

Forcing Youthful Gene Expression in Old Cells Should in Principle be Beneficial

It is reasonable to expect that forcing the epigenetic regulation of gene expression in cells in old tissue into a pattern more like that of cells in young tissue could be beneficial.

Some of these changes in gene expression are clearly entirely maladaptive and detrimental to the health and life span of the organism. All else being equal, reversing those changes, and only those changes, will in principle lead to improved health. In principle is one thing, but will the effect size be large enough in practice, however?

Read More https://www.fightaging.org/archives/2021/02/forcing-youthful-gene-expression-in-old-cells-should-in-principle-be-beneficial/

Calling for a New Field of Gerobiotics to Reverse the Aging of the Gut Microbiome

The gut microbiome is a complex, ever-shifting collection of microbes that mediates much of the interaction between diet and health. This microbiome changes with age.

The exploration of these changes is still a comparatively young field of research, even while expanding considerably in recent years. As we age, some of the beneficial species that produce useful metabolites decline in number, while some of the harmful species that can cause chronic inflammation prosper and expand.

Chronic inflammation is an important aspect of degenerative aging, driving development and progression of all of the common age-related conditions.

Read More https://www.fightaging.org/archives/2021/02/calling-for-a-new-field-of-gerobiotics-to-reverse-the-aging-of-the-gut-microbiome/

Cellular Senescence in the Aging Retina

Senescent cells are created constantly, but only begin to linger and accumulate in tissues in later life, as the pace of creation accelerates and the mechanisms of clearance decline in effectiveness.

A senescent cell secretes a mix of moleculers that spurs chronic inflammation and disrupts the processes of tissue maintenance and function.

Read More https://www.fightaging.org/archives/2021/02/cellular-senescence-in-the-aging-retina/

Protein Signatures of Aging Suggest a Slower Pace of Aging in Centenarians

Researchers here build a signature of aging based on age-related changes in the proteins found in blood samples, and then show that centenarians appear to undergo these changes more slowly than people who die at younger ages.

Read More https://www.fightaging.org/archives/2021/02/protein-signatures-of-aging-suggest-a-slower-pace-of-aging-in-centenarians/

The Gut Macrobiome in Chronic Inflammation and Aging

In recent years, a great deal of attention has been devoted to the role of the gut microbiome in aging, as populations shift to include fewer helpful and more harmful microbes. In particular, the ability of the gut microbiome to influence the state of chronic inflammation in aging may be at least as important as lifestyle choices such as degree of exercise.

Expanding this line of thinking, researchers here look at the macrobiome, small parasitic animals that dwell in the gut, and their role in age-related inflammation.

Read More https://www.fightaging.org/archives/2021/02/the-gut-macrobiome-in-chronic-inflammation-and-aging/

The Goal of Geroscience is Life Extension

It is only comparatively recently that the research community has become supportive of efforts to treat aging as a medical condition, with researchers able to publish and speak in public on the topic without risking their careers.

Even so, few researchers in this more receptive environment have been willing to be clear that the goal of treating aging is to greatly extend healthy life span, not just improve health within the life span we presently enjoy.

Read More https://www.fightaging.org/archives/2021/02/the-goal-of-geroscience-is-life-extension/

Large Body Size in Mammals is Accompanied by Duplication of Tumor Suppressor Genes

Larger mammals have many more cells than smaller mammals, and cancer risk increases with cell count, all other things being equal.

Between species, body size does not correlate with cancer risk, however. Since species such as elephants and whales do not suffer an enormous rate of cancer in comparison to humans, clearly there are important differences in cellular biochemistry between these species.

Read More https://www.fightaging.org/archives/2021/02/large-body-size-in-mammals-is-accompanied-by-duplication-of-tumor-suppressor-genes/

A Profile of Repair Biotechnologies, Working to End Atherosclerosis

Repair Biotechnologies is the company I founded with Bill Cherman a few years ago, to work on interesting projects in the rejuvenation biotechnology space. Time flies when one is busy.

Our primary focus these days is the development of what we call the cholesterol degrading platform (CDP), a technology that does exactly what one would expect from the name. Localized excesses of cholesterol – and particularly toxic, altered forms of cholesterol – lie at the root of numerous serious medical conditions, and contribute to a lesser degree to many more.

Read More https://www.fightaging.org/archives/2021/02/a-profile-of-repair-biotechnologies-working-to-end-atherosclerosis/

Profiling the Work of the SENS Research Foundation

The SENS Research Foundation is focused on enabling progress in neglected areas of science that can be applied to the development of rejuvenation therapies.

The SENS rejuvenation research program is based on periodic repair of the forms of cell and tissue damage that are known to lie at the root of aging, damage that accumulates over time and is caused by the normal operation of metabolism.

Read More https://www.fightaging.org/archives/2021/02/profiling-the-work-of-the-sens-research-foundation/

Failing Autophagy and Mitophagy in Alzheimer’s Disease

The processes of autophagy break down and recycle damaged or unwanted structures within cells. Mitophagy is the specialized form of autophagy that clears malfunctioning mitochondria.

Read More https://www.fightaging.org/archives/2021/02/failing-autophagy-and-mitophagy-in-alzheimers-disease/

Correlating Cancer Risk with Epigenetic Age

Epigenetic clocks measure changes in epigenetic marks on the genome that correlate with age. Greater epigenetic change at a given chronological age indicates a greater burden of biological aging, more damage and dysfunction.

Read More https://www.fightaging.org/archives/2021/02/correlating-cancer-risk-with-epigenetic-age/

Inhibition of GLS1 Selectively Destroys Senescent Cells

Senescent cells accumulate with age, and this accumulation is an important cause of age-related dysfunction and disease. Clearing senescent cells from old animals produces rejuvenation, and human trials of first generation senolytic drugs capable of selectively destroying senescent cells are underway for a number of age-related conditions.

Read More https://www.fightaging.org/archives/2021/02/inhibition-of-gls1-selectively-destroys-senescent-cells/