My intention here is to share some new insights I have had as a longevity scientist, ones highly relevant to people who regularly take 4 Herb Synergy.  In short, new science indicates that the supplement is very likely to confer a very significant longevity bonus.  This conclusion is based both on my deepest understanding of the biological mechanisms of aging, and my direct personal experience.

A personal note, to start: I now believe that 4 Herb Synergy has a lot to do with my functionality, vitality and capability to continue with all key areas of my life, be they social, family or professional.  Turning 94 in 2 months I am now about as heathy, functional, and professionally active as I was 40 years ago, and I expect this situation will go on until I am well beyond 100.  Moreover, I think the 4 Herb Synergy supplement can significantly contribute to other generally healthy people likewise realizing extraordinary longevity.  This blog is concerned with the scientific why and how of that.

True, for 15 years now my profession has been a longevity scientist, seeking to understand what aging is and how it may be slowed, stopped or reversed.  True also, I am the inventor of 4 Herb Synergy (4HS), and am now a Partner along my son Michael in the LLC Synergy Bioherbals.  But until March of 2023 I never closely connected these two thrusts of my activities. I knew 4HS was good for alleviating the aches, pains and symptoms of my inflammatory conditions.  I needed to use it and saw clear benefits from doing so.  But I had never considered 4HS as a longevity intervention, nor have I ever characterized it as such in my writings.  This perception changed radically for me in April of this year, 2023, when the fruits of my aging research came together sufficiently to allow me with confidence to understand adult aging: what causes aging, how it works, what its phases are, how it shows up in everything living thing.  And, along with understanding aging, identifying what we can practically do to greatly slow aging down.  That’s the story I tell here.

Understanding Aging

Understanding aging opens up the possibility of identifying strategies for slowing aging down, possibly stopping or even reversing it – extremely exciting for me as well as for some other aging science researchers who also grasp this possibility through their own work.  The good news is that aging, being a program, can be hacked.  For humans I know of one effective hack applicable during the final phase of aging, probably good for extending vibrant health and functionality of nominally healthy individuals to beyond 100 years of age.  It is the hack I have been personally pursuing and 4 Herb Synergy plays a central role in it.  Aging is a biological program that proceeds lifelong in phases, from embryogenesis to a final phase whose actions kills everybody left.  This is a very ancient program, manifest in the earliest living creatures, and evolutionary conserved thereafter. Versions of this program operate in every living creature – plants, bacteria, worms, insects, fish, snakes, lizards, and all mammals including us humans.  There is a species-determined version of the aging program and corresponding maximum lifespan for every living thing – 123 years for humans.

The final phase of aging turns deadly to kill every living thing off by the absolute age limit for the species – no exceptions.  Next, I will fundamentally characterize the central process of aging, it’s purpose, what it does, its stages, how it works, and what causes it.  Then, I will go on to describe a major hack on aging, one I think is good for average human life extension of 20% to 25%. Far more than the 5% to 12% known for various specific life-extending interventions, like taking rapamycin.  I believe this hack can probably postpone the death-sentence action of the aging program by 20-30 years for us humans, and can likely allow most people to remain highly active, healthy and functional until 100 or more.  It is the hack that has been working personality for me.

The science of aging is wickedly complex and here I can present only a central outline of what is supported by thousands of research studies, necessarily simplified, though still accurate.  I have recently published an article in my agingsciences.com blog covering the same ground covered here from a much more technical perspective. It contains links to numerous, published science literature citations that back up assertions I make here: www.anti-agingfirewalls.com/2023/04/04/healthy-active-and-productive-till-100-laying-out-the-adult-aging-process-a-breakthrough-and-my-personal-story.

What is aging?

Aging is a carefully articulated biological program that proceeds from conception to death, in phases.  This program is very ancient and is “evolutionarily conserved,” which means it responds to a key biological necessity and versions of it are in every living thing.  Evolution has passed this program on to new species as they evolved. (In creating any new species, evolution prefers to re-use and adopt solutions it has already contrived and found workable, rather than invent them anew.  That is why we have variants of the same organs found in tiny field mice, whales, skunks and elephants.)  Species-specific variants of this aging program operate in essentially all known species, be they bacteria, insects, plants, fungi, mammals.  Every species has its own “use by” expiration maximum lifespan.  For humans 123 years, for many mouse species 20 months, for fruit flies 10-20 days. The Mayfly has a lifespan of only 24 hours and completes its life cycle, including reproduction, within one day of its birth.  Evolution loves all living entities, and generally seeks to provide for the wellbeing and competitive survival of each.  However, evolution loves living species even more. In cases where individual survival and species survival are incompatible. evolution/nature picks the path of species survival.  That, I think, is why the final stage of aging is out to kill off every living entity by its species expiration date.  That way, younger members of a species don’t have to compete for resource too long with ensconced older members, and even the most horrible and controlling of dictators pass away in time.  Aging is how nature implements its drive to best insure the survival of biological species.  Species may survive up to millions of years.  Lifespans of members of most all species are less than our own.  A few species of trees have lifespans of more than a thousand years.

Forget living forever in your present body.

Absolutely everything about us as individuals is temporary.  I do believe we are now in an extremely important decade in the history of biology, however, one in which we are now decoding many mysteries of life, learning how to reverse key aspects of aging, and learning how to expand lifespans of healthy individuals, possibly up to hundreds of years.  In my research writings and presentations, I have referred to this process as “YOUNGING” You can find out about much more about it by searching on Internet for this term together with my name.  Look for sound podcasts and YouTube videos as well as written treatises.

Several other longevity scientists have also been working on YOUNGING interventions and have demonstrated how their interventions can make old rats younger in most important dimensions.  YOUNGING, effective age reversal, has been proven possible!

Aging impacts all levels of every organism known: biochemical, sub-cellular (including mitochondria), cellular, organ, major system and whole organism.  Most of the science literature on aging has focused on particular impacts, “Hallmarks of Aging” at particular levels, leaving confusion as to what is secondary vs. what is basic and causal.  The fundamental cause of aging is much simpler.

It is a distinct effective program of aging that proceeds in phases, including the program of initial and early development starting with an egg and a sperm.  The essential features of this aging program have become clear to me, but this has only happened recently.  This program is out to grow us up successfully until we are 25, + or – a few years depending on individual.  It is working for the good of the species not the individual.  Lifelong until the final phase, it strives to ward off serious infectious diseases and other deadly pathologies. In its final phase, when we get to be 80 and beyond, the program it is out to kill everybody by age 123.

Through most of our lives, the aging program works to keep us healthy.  However, if the program can’t manage to do that, it can quickly change its strategy to having your own immune system kill you instead. It does this by loosening a deadly inflammatory cytokine storm. This is to keep people whose condition is too weak to fight off a pathogen from passing that pathogen on to others, accelerating its propagation. It is an example of how evolutionary processes favor survival of a species over survival of an individual when these two objectives are in conflict.  This program is very ancient and versions of it exist in all living species include plants, birds, bees, cows, worms, insects dolphins, and mushrooms. It is just as efficient and effective as the early development program is.  But, being a program aging can be hacked, once one knows exactly how it works. I know of one easy main hack that I think can buy us an 20-30 or more years of additional healthy active lifespan.  It works by slowing the aging program way down.  It is available to everybody right now and inexpensive.  I know. I am nearly 94, and what I am proposing here has provided me with the wherewithal to lead a full active family and social life, conduct deep research in the biomedical literature, attend to Synergy Bioherbals LLC, and generate and publish this blog.

The aging program typically proceeds in Phases.  The early ones are focused on initial stages of growth and development starting with conception.  The finial stage is plain out to kill you one way or the other

THE STAGES OF THE AGING PROGRAM

Let’s look at how aging typically plays out at various stages of life of a healthy disease-free person in a modern industrialized society, namely at Conception and at ages 1, 25, 45, 68, and 85.

Conception

Early development including embryogenesis the first stage of aging and is probably the most complex and remarkable natural process known in all of science.  Starting with an ovum and a sperm, it leads to a human body comprising some 37 trillion cells of 200 types, organized to support the complexity of organs and body systems we all have.  It is a precisely articulated process involving many stages which has been extensively studied.  The fine details of it would fill libraries.  All cells in a human body have the same genes.  The differences between the 200 cell types we have are epigenetic, a function of which genes are turned on (expressed, that is actively make the protein corresponding to that gene) and which are turned off in any particular place in a human body at any given time.  This first year of human development is an exquisitely choreographed and very reliable process involving multiple steps of turning dozens, hundreds and thousands of development and other genes on and off in an extremely complex and highly specific manner.

How does the developing embryo go about turning a closely related family of genes off and on together to achieve a development step, say growth and development genes?  A big part of the answer is via histone methylation/demethyation.  Histone methylation/demethylation is a major tool used by the body in early development to turn large and small families of genes on and off together.  That is attaching or detaching methyl chemical groups to histones, the “spools” around which DNA is wrapped.  For most of the histones, genes in a highly methylated histone spindle are turned off, cannot be expressed.  De-methylating the histone turns the genes on.  For some histones the opposite is so.  Many of the genes in our chromosomes are carefully sequenced so this simultaneous turning on and off of highly related genes can happen.  It happens to be that many growth and development and maintenance genes are associated with the histone H3k27.  To telegraph where I am going here, the same basic mechanisms of histone methylation and demethylation for turning off or turning on hundreds or thousands of genes at once are used in all stages of the aging program throughout life.  There is also a complex end-of-life phase of the aging program that kills everybody by age 123, and that phase of the aging program also uses histone methylation to turn groups of genes off and on.

AGE 1

The initial Developmental Phase of the program has been at it during the pregnancy period and for a year after birth., has accomplished much but still has a long way to go.  Again, our bodies are the most complex structures known to exist in the universe, and this development process is probably the most complex natural process known.  Continuing with a simplified but correct description of what is most relevant here: during the early phases of development there is a high degree of organ-specific expression of JDJM3 and UTX, the demethylases that keeps double and triple methylation from happening during development at histone position H3k27. This is necessary to allow full expression of large numbers of growth and development genes as well as maintenance and repair genes.  There are also times and places during early development when these deacetylases are turned off.  At age1 there is still a lot of growth and development to be done.

AGE 25 (+/- 3- 5 years depending on the individual.)

This is the typical age when the Development Program gives way to the Adult Aging Program in humans.  This transition can be noticed in many species, including plants.  In some species it can occur very rapidly, taking place in a few hours.  In many species, it occurs just after the initial phase of offspring-bearing.  The transition involves lowering of expression of JDJM3 and UTX, the demethylases that keeps double and triple methylation from happening during development at histone position H3k27.  At the time of transition, the Polychrome Repressive Complex (PRC) starts its adult job of inducing double and triple methylation at H3k27me2-3, slowly at first.   This and methylation changes at other histone positions have net impact of starting to down-regulate numerous repair, maintenance and renewal genes.  Yet at this age the expression of these genes is still near maximal.  There is little to no tissue damage or consequent inflammation.  As we know many people at this age are very healthy and think and often behave as if that situation will go on forever.  Diseases are generally rare and tend to resolve quickly.

AGE 45

The PRC has been doing its methylation job for 20 years now.  So many key repair, renewal and maintenance genes are significantly down-regulated.  With the down-regulation of these genes and tasks they perform, some tissues begin to be distressed, become inflamed and start emitting inflammatory cytokines like TNF-alpha,IL-1, IL-6 and IL-22.  Systematic inflammation is more manifest.  Diseases and sicknesses and signs of aging of all kinds are becoming more common and more of concern, including arthritis, pneumonia, near-sightedness, obesity.  Yet, despite partial methylation, body repair, maintenance and renewal genes are still generally active enough to support largely good functioning.  Hallmarks of aging are evident and the person looks like a 45 year-old, no longer like he/she looked at 25.

YES, AGING IS NOT DUE TO ACCUMULATION OF RANDOM DAMAGE. IT IS DUE TO PROGRESSIVE DOWNGRADING OF NATURAL DAMAGE REPAIR AND RENEWAL PROCESSES DUE TO PROGRESSIVE DOWN-REGULATION OF KEY GENES.

AGE 68

The Adult Aging Program has been at work some 43 years now.  DNA histone methylation is now such that body repair, maintenance and renewal genes are functioning at a fraction of there original levels.  They are too methylated.  And some developmental genes that produce unwanted actions for aging adults are being progressively turned back on.  Multiple tissue types and organs are experiencing increasing distress, and are emitting copious levels of inflammatory cytokines which persist in the bloodstream.  These increases the gene methylation levels even further, a positive feedback reaction.  The overall body is going into a hyper inflammatory state.  And incidences of the inflammatory diseases the kill old people are becoming frequent: cancers of all types, retinopathy, inflammatory lung diseases, dementias, coronary artery and valve diseases, auto-immune diseases like arthritis, lupus and scleroderma, gout, etc.. The “usual suspects” for killing old people.  Several such diseases can occur at the same time.  People at this age are more prone to catching infectious diseases like SARS or COVIDs, and use of the health care system is typically accelerating.  Heart attacks and strokes are becoming common.  Many friends in the same age cohort are moving into Assisted Living; some are going into nursing homes.  Emergency Room visits are becoming more commonplace.  Some family members and dear friends are starting to die.

AGE 85

The situation described for age 68 has become much more dire in every respect.  Histone and DNA methylation are at levels where many repair, maintenance and renewal genes are close to being completely silenced. DNA methylation and circulatory inflammatory cytokine levels seem hopelessly abnormal.  A positive feedback loop of whole-body hyper inflammation leading to ever more unwanted DNA histone methylation has taken over.  Tissue and organ damage are extensive, and the diseases of old age are rampant and doing their pre-killer and killer jobs.  Far less than 30% of the population makes it to this age.  And if you do manage to live that long, your general outlook is not good.  From this age onward, you are likely to experience increasing frailty and multiple emergency room visits and hospitalizations.  You may pass the final months or years of your life in a nursing home with dementia, a semi-functioning heart, and an incurable cancer.  there are more than 100 types of cancer that can affect almost every part of the body.  Aging can (and does) kill you in thousands of different ways.  Organ and system failures and diseases are among the most common. 100% of the time, “All the King’s Horses and All the King’s Men,” of medicine and health care can’t rescue you from the final Death Phase of the Adult Aging Program.  A version of the Adult Aging Program works for every advanced species we know of.  Everything alive dies, no exceptions.

Let me contrast my personal situation at 94+ with the grim scenario for 85 year olds listed above. I have none of the known degenerative diseases of advanced aging.  I haven’t seen a real doctor for 9 months.  Last time I was hospitalized (for 1 day) was near a year ago and that was because of broken ribs due to a freak accident.  I can walk for miles, mow my acre of lawn, chase my little granddaughters and grandsons around the back yard, cook up pasta Bolognese for the whole family, vacuum key areas of the house do the laundry and wash a sink-full of dishes and load the dishwasher every night. And get in 6-12 hours of longevity research, communications with colleagues and writing every day.  Unlike some of my close colleagues I only monitor a tiny collection of health and aging biomarkers.  For the same reason most people in their 30s and 40’s doesn’t bother with their biomarkers – they don’t have to.

HACKING THE AGING PROGRAM

Being a program that we can understand, aging is at least partially amenable to hacking.  I believe I have described the central causal chain of events involved in human aging. And those events allow us to identify with confidence how to slow advanced aging.  The aging program can be hacked, basically by blocking the hyper-inflammation part of the positive feedback loop in the final phase.  My main intervention for blocking systemic inflammation in the last ten years has been regularly taking 4 Herb Synergy – a nano-preparation of certain herbal anti-inflammatory dietary supplements.  As below, I also do a lot of other things to lower systemic inflammation.  I am sure some of these are important, but I don’t know how important.  What I can say is that if I discontinue taking 4HS, in 3-4 weeks, I start getting distressing inflammatory symptoms which get worse and worse.  Resuming 4HS, these symptoms vanish in a week or so. Discontinuing other anti-inflammatory supplements or activities for up to 1-2 months while still staying on 4HS, I have not noticed any strong negative effects.

Other researcher Findings

Other researchers have suggested a variety of other strategies, all of which have the impact of blocking chronic inflammation.  Irina Conboy, a prominent aging researcher, and her colleagues have suggested periodic purifying of circulating blood from the pro-inflammatory cytokines using an apheresis machine. Apheresis involves the removal of blood plasma from the body by the withdrawal of blood, its separation into plasma and cells, purification of the plasma, and the reintroduction of the cells and purified plasma into the body.  Her small-animal experiments suggests that that process also works for the reduction of circulating inflammatory cytokines.  Her aged small animals by multiple measures get younger.  While it works, apheresis is not practical for most people. because it is expensive, invasive, requires technical expertise and the use of a special machine. Further, for apheresis it to be effective in keeping the bloodstream free of inflammatory cytokines, the process must be repeated every 3 weeks or so.

Approaches to elimination of inflammatory cytokines in the interest of YOUNGING used by other researchers include:  injections of exosomes derived from young pig blood plasma, and treatment with GDF11, a strongly anti-inflammatory blood factor. I will not discuss these further here since they cannot be practically pursued by ordinary people.  What is important is that multiple approaches to reducing chronic inflammation done by several research groups have been shown to effectively initiate YOUNGING in mice or rats.

Other strategies I have been using to combat systemic inflammation

I list the most important of the additional anti-inflammatory strategies I have been pursuing here.  I have discussed each of these in detail in articles in my longevity blog agingsciences.com.

• Taking additional anti-inflammatory additional supplements in pill form, such as NRF2 activators like gingko bilboa, milk thistle extract, saw palmetto, and bacopa,
• Taking a quality fish oil supplement, one that is high in DHA and EPA. These oils contain key substances important for the resolution phase of acute inflammation to occur, the normally final stage where the inflammation vanishes. The substances are called resolvins, protectins, maresins and lipoxins,
• Taking supplements like nicotinamide riboside to upgrade the expression of the NAD+ metabolic factor, upregulating a number of protective genes,
• Taking supplements intended to improve mitochondrial electron transfer chain functioning,
• Synchronizing to critical brainwave frequency Via Pulsed Electromagnetic Frequency (PEMF) devices, which helps me concentrated better during days and sleep better at night,
• Selective partial body irradiation with critical infrared frequencies,
• Deliberate exposure to whole-body heat conditions (EG, sauna) and cold exposures, to upregulate expression of heat shock and cold shock proteins,
• Exercising while breathing oxygen, a process known as EWOT,
• Living and interacting constantly with significantly younger people, and
• Getting ample solid REM and Deep sleep on a regular schedule.

These are all interventions that I have researched and know are powerfully anti-inflammatory.

Acute vs Chronic Inflammation

The inflammatory process is an essential first-line immunologic defense system evolved in advanced organisms to confer protection required for survival of individuals.  Short-term acute inflammation is part of wound healing and acts against harmful agents, such as pathogens, toxins, or allergens.  Familiar manifestations of it are the itchy red bumps of mosquito bites, fever when you have the flu, and redness and swelling associated with burns.  Less familiar ones can include muscle weakness, diarrhea, nausea, joint pain, and skin rashes.  Normal inflammation involves a number of distinct phases, including a final resolution phase.  “Under normal conditions, the tightly coordinated actions of various defense components including immune cells, endogenous anti-inflammatory agents, and tissue remodeling processes enable the resolution of acute inflammation by facilitating the elimination of pathogens, infected cells, and repair to damaged tissues to restore body homeostasis [1]. However, when this intricate acute inflammatory response fails to resolve and instead persists, more defense components are mobilized to create a long-term unresolved immune response known as chronic inflammation. Chronic inflammation, which typically manifests itself in a low-grade manner for a prolonged period, involves macrophage- and lymphocyte-accumulated leukocytes [2], and various other cellular components. It is important to recognize that this chronic inflammation is causally associated with changes in the cellular redox state and cell death signaling pathways.”  So, Chronic inflammation is inflammation that does not resolve. In this discussion of longevity, by “systemic inflammation,” I am referring to chronic whole-body inflammation.  This discussion highlights how systematic inflammation is both caused by and causal of epigenetic aging.  Some drugs (like prednisone) tend to block both types of inflammation.  They can be used only for short periods because acute inflammation is an important tool of natural body protection.  4HS blocks chronic inflammation while still allowing acute inflammation.  As a long-term user of 4HS, I have an intact and strong wound healing capability, meaning I can respond with acute inflammation when needed, while controlling my systemic inflammation.

ANSWER TO A KEY QUESTION

The new perspective of this article answers a central question I have been asking myself for years.  That is: Which of the longevity interventions that I have been pursuing in recent years have been efficacious in allowing me to be essentially disease free, cognitively sharp and still highly productive as I grow older, now approach age 94?  Which one or ones are central?  The answer is the interventions that combat systemic inflammation, in my case the main approach having been regular taking of 4 Herb Synergy during the last seven years, and for the twenty years before that, taking the 4HS herbal anti-inflammatory components. And this was done with a different intent than longevity in mind.