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Telomeres, Telomerase and Senolytics

Telomeres, Telomerase and Senolytics

Telomeres, telomerase and senolytics is ushering in a new era of longevity medicine and vital health.   These are exciting times.

In 1994 the first ever world conference on Anti-Aging Medicine was held in small “off the strip” hotel in Las Vegas.  An exciting prospect under the auspices of American Academy on Anti-Aging Medicine (A4M).  The goal of that time was to aggregate the best of medical science and information into a cohesive body of high-tech preventive medicine.  With the aim of prolonging life and health span.  It was a heady proposal with its share of critics.  It was the beginning of a new paradigm.

So many terms have been used over the years, including Integrative Medicine, Complementary Medicine, Functional Medicine, Anti-Aging Medicine, Age Management Medicine and Longevity Medicine.  They share one common goal.  Improving optimal health and well-being and increasing a healthy lifespan — HealthSpan.

It is all based on optimizing physiological function and cellular health and vibrancy.  Through the use of micronutrients, vitamins, minerals, hormone replacement therapy, rational and scientific approaches to exercise, our focus has always been directed toward a higher goal.

Nutritional Medicine Pioneers

There have been a series of widely acclaimed nutritional constructs.  Starting with Nathan Pritikin and Julian Whitaker’s advocacy of complex carbohydrates, to Michael and Mary Eades advocacy of high-protein diets (Paleo), to Dean Ornish vegan diets, to low carbohydrate diets most successfully advocated by Robert Atkins.  Enter David Asprey of Bulletproof fame with refinements and banner success.    Each rock star has held center stage in their time.

So where are we today?  The current consensus is a low carbohydrate, ketosis generating diet with healthy fat intake as the most beneficial pursuit.  This can be elaborated elsewhere.

The Holy Grail throughout human history, has been the search for eternal youth and immortality.  The Shangri-La effect.  In the modern age, we have been seeking “the master controller” of aging. Does this exist?  Is there one gene or one gene locus that controls aging?  We are closer to some vital answers.  And our efforts have increased dramatically in the last 20 years and even more so in the last 3 to 5 years.

We have shifted from Anti-aging Medicine to full Regenerative Medicine.  What I term Anti-Aging 2.0.  A shift from high-tech preventive medicine to truly regenerative therapies.  Now what form does this take?

Epigenetics Controls our DNA

Since the discovery of the structure of DNA by Watson and Crick (which should have been Linus Pauling and Rosalind Franklin), we have all been inured in the concept that genetics controls everything.  But are we slave to our genetics?  The answer is no.

The concept of nature or nurture was used to explain why genetics is not the master arbiter.  Or incomplete penetrance with age.  But exciting re-thinking of genetics has led to the new field of Epigenetics.

We now know our DNA is merely a blueprint.  A blueprint alone cannot build a house or skyscraper.  Architects, general contractors and workers execute the master blueprint.

So the field of epigenetics is an effort to explain how various interactions and signaling processes turn on or off master genetic controllers or suppressors.  And … who controls the controllers?

Balance is the goal

The most important concept to keep in mind is balance throughout our life.  There is always the process of “blastic” vs. “clastic” activities.  A blastic activity build muscle and bones whereas is “clastic” activities clear away old dead tissue.  Our bones throughout life are constantly being remodeled.   Hormones must be balanced.

This higher level of balance throughout life is delicately controlled by repressor or suppressor genes or expressive genes.  As we age, this balance is subject to environmental and psychological stress, foods, EMF, chemicals, inflammation, oxidation and glycation.   Such is our modern environment.

Telomeres and Telomerase Hold Great Promise

There are two highly innovative threads of exciting research and experimentation in small innovative groups.  Telomeres and telomerase is based on the concept that our DNA loses ability to replicate at a cellular level because of frayed end caps.  The telomeres.  This explains the vaunted Hayflick limit — that cells cannot divide indefinitely.

Teleologically a specific gene (hTERT) controls the expression of telomerase that can repair these end caps by lengthening our telomeres.  It is not normally expressed.  It does seem to be expressed in high amounts in tumor cells, but not all.  And it is expressed in the germ cell line — the immortal cells that we pass from generation to generation.

Senolytics — Clearing Senescent Zombie Cells

At the other end is a highly dedicated group of experimenters and researchers in the rapidly expanding field of senolytics and senescent medicine.  Ergo the SENS project by Aubrey de Grey. Based on the concept that as we age, we accumulate more and more “zombie cells”.  These are senescent cells that lose vital function, but “hang around” expressing inflammatory and potentially toxic influences.

If we could only clear these senescent cells, the current thinking is revitalization and growth of healthy, normal cells is enhanced.  This is a simplified view worth expanding in later blogs.

Mayo Clinic Research with Dasatinib and Quercetin.

The Mayo Clinic has conducted seminal research and experiments with Dasatinib and Quercetin (D&Q) in mice studies showing significant repair of the aging process.  Further work with senolytics has been carried out at the Buck Institute in Marin.  Now we know there are additional Senolytic agents including Fisetin and Rapamycin.  When used in small doses at infrequent intervals, experiments have shown either age regression or repair of aging effects.

Telomerase and Senolytics  – A Unified View

The most elegant approach to synthesizing these major trends and pathways is to visualize a continuum.  Combining the effects of telomeres, telomerase and senolysis.

Telomere shortening and effects with age
Telomere shortening and effects with age

As we age, there is a critical time that no one has specifically identified where genomic instability is most critical.  I think this is probably at age 50-60 years of age.  At this critical juncture cells could be rejuvenated with telomerase inducers or senolytics, thereby preventing cancer progression and enhancing regeneration and rejuvenation.   I want to thank Michael Fossel for the kind use of this most powerful graphic.   His work at Telocyte is really exciting.  Start by reading his latest book — The Telomerase Revolution.  And even today more late breaking stories from Marie Blasco’s lab in Madrid

I am synthesizing this unified theory and vision of age regression and regenerative therapies.  Can we now think about living to 120 or more?   What are the challenges? You can start by reading the weekly blog by “Reason”: fightaging.org.  Future blogs to expand this discussion in more detail.

Calling all seekers and discoverers.   A video production will be available soon.

Philip Lee Miller, MD

Carmel, CA

Oct 2019

My Daily Personal Nutrition Routine

My Daily Personal Nutrition Routine

People ask me what is your personal nutrition routine?  What do you take on a daily basis? What supplements and micronutrient do you take yourself for optimal nutrition? To achieve optimal health and well being in a high stress world today.

Personal Goal

A personal goal and my mission for all of you is health and well-being. Longevity with vigor. Protection from cognitive decline. Prevention of diabetes, arthritis and cardiovascular disease.  Growing older without aging.

It was the famous British physician Sir Thomas Sydenham who said.

” you are as old as your arteries.”

Arterial health is a major goal. This is why we strongly advocate CIMT imaging of your carotid arteries here in our office.

My daily routine starts upon arising (on an empty stomach) with fat soluble nutrients.  This includes:

  • 1 tbl of fish oil
  • Vitamin E 1200 units
  • Vitamin K2 15,000 mcg
  • Vitamin D3 10,000 units
  • Thyroid
  • Phosphatidylserine 300 mg and
  • Nattokinase 100 mg to prevent heart attacks and strokes.

These fat soluble nutrients are more efficiently absorbed with fish oil.  They are taken on an empty stomach so they do not interfere with oatmeal for breakfast.

There is a 45 to 50 minute hiatus.  Read my morning emails.  A morning shower after which I apply my first dose of testosterone cream.

Breakfast

Breakfast starts with Bob’s Red Mill gluten-free oatmeal. Cooked to a creamy consistency over a gas stove. Now my first highly fortified protein shake of the day.

  • 2 scoops of whey-based protein
  • 1 tsp (3 grams) of carnitine tartrate
  • 1 tbl phosphatidylcholine
  • 1 scoop of d-ribose
  • l-deprenyl for cognitive enhancement

This is the most efficient and richest source of high quality protein. The protein shake can be mixed with Odwalla orange juice or your favorite base.

Breakfast is fortified with an array of vitamins and micronutrients.

  • Selenomax 200 mcg
  • OptiZinc 30 mg
  • Nutrient 950 multivitamin
  • DHEA 50 mg
  • Diaxinol
  • 4Sight
  • Vitamin B2
  • Methyl folate 1600 mcg
  • B12 10,000 mcg
  • Alpha lipoic acid 300 mg
  • Ginkgo Biloba 60 mg
  • ProBiotic 100
  • Vitamin C as ascorbyl palmitate
  • “Reacted” chelated Iron 58 mg (read my previous series on iron)

It’s quite a handful, but each of these is designed to improve immune function, cardiovascular function, energy and cognitive vigor.

Lunch

Lunch is a very sparse affair with my second protein shake of the day.

  • 2 scoops of whey-based protein
  • 1 tsp ( 3 grams) carnitine tartrate
  • Gluco-shield.

It is a quick and efficient source of energy.  This carries me through the day until 5:00 or 6:00 pm.

Dinner

Dinner is a rich source of protein including fish, chicken or organic beef with some vegetables, most especially broccoli and carrots. My preference at night is a combination of chocolate Rice Dream and chocolate Hemp Milk.

At night I might cheat with a tiny source of extra carbohydrate. The goal is always low carbohydrate, high-protein. This is not a ketogenic diet.  It is a modified Paleo diet.

Ketogenic diets do promote weight loss. I am still concerned about the quality of fats being advocated in ketogenic diets.  Usually including large amounts of butter, cheese, bacon, sausage and other sources of potentially inflammatory Omega-6 oils.  Omega-6 fats potentially increase arachidonic acid which promotes a cascade of inflammatory metabolites.

This is the source of another blog soon.

Dinner is also supplemented with:

  • Nutrient 950 multivitamin 3 caps
  • Diaxinol 1 cap
  • 4Sight 1 cap
  • Ginkgo biloba 60 mg
  • Magnesium 400 mg
  • Alpha lipoic acid (a stellar antioxidant) 300 mg

Bedtime

Just before retiring at night I take

  • Magnesium 200 mg
  • Nattokinase 100 mg

Coda – Ask Jack

Jack LaLanne at age 60. Original fitness guru
Jack age 60

Does that sound like too much? We could have asked Jack LaLanne. Our supreme nutrition and exercise experiment. He took all known supplements and micronutrients for well over 70 years.

Jack once said, “I can’t die, [he most famously liked to say]. It would ruin my image.”

I can remember Coach Dees in high school. He was our cross country coach.  On the first day he said, “Now I want all of you to go out and start drinking wheat germ oil.”   This was 1960 when you went into a tiny proto health-food store with an old guy sitting at the bar drinking carrot juice.  Wheat germ oil was supplied in plain unattractive brown bottles.   It was my first source of concentrated Vitamin E.

In Medical School at UCSD a group of us would read Adele Davis.  Then Linus Pauling started writing about OrthoMolecular Medicine.  He was advocating therapeutic, supra-physiologic doses of vitamins, minerals and selected micronutrients.

It’s been a life-long quest.

We all want healthy and robust longevity in a chaotic world. The ultimate goal of the preventive medicine physician is to set an example and show the way.

Thank you for reading. Now what are you taking? Drop me a line. Don’t forget your Fullscript source of all supplements and micro-nutrients.  Then read (or re-read) my bestselling book.  The Life Extension Revolution.

Philip Lee Miller, M.D.

Carmel California

Not So Random Thoughts on Aging

Not So Random Thoughts on Aging

Baby boomers and aging

Why Are Baby Boomers Dying Prematurely?

I am a pioneer antiaging/age management physician.  I co-authored the best-selling book on the age management – The Life Extension Revolution: the New Science of Growing Older without Aging. I was the founder of the Los Gatos longevity Institute rebranded as California Age Management Institute. These credentials are well known.

I have been giving serious thought and reflection on an alarming dichotomy of generations. It appears that so many individuals who were born in the 20’s and came of age during the Great Depression and World War II are living well into their 90s. They are living forever. I have wondered what is it that promotes this longevity?  This even includes survivors of horrific POW and Concentration camps.

Meanwhile, baby boomers are dying prematurely in their 50’s, 60’s, and 70’s. Notable names like Leon Russell, Glenn Frey, Tim Russert. The list grows every day.

At first I thought these were all entertainers. Like the premature death of Jim Morrison, James Dean, Andy Kaufman, Marilyn Monroe, Jerry Garcia and Janis Joplin.  But I have also seen a number of my own medical school classmates pass well before their time.

So what is it about those who grew up and came of age during the Depression and World War II?

They lived a less stressful life. There were no microwaves, cell phones, television, DVDs, Internet, computers. Before there was traffic congestion with cosmopolitan smog and more recently invisible and lethal EMF smog. They ate sparsely. They ate healthy foods that were enriched in non-depleted soils. From “victory gardens.” They did not overeat because there were no fast food restaurants. Modified caloric restriction.  Food was expensive.

Generational Age Categories

An interesting headline published by the WJ Schroer shows these descriptive categories.

  1. Depression-era — born 1912 – 1921
  2. World War II — born 1922 -1927
  3. Post-War Cohort — born 1928 – 1945
  4. Baby boomers — born 1946 – 1965 (early and late waves)
  5. Gen X – born 1966 – 1976
  6. Gen Y or Millennial’s – born 1977 – 1994
  7. Generations Z – born 1995-2012. These are not Millennial’s. These are the victims of the most recent Florida shooting.

Each one of these generations is characterized by an ethos and environmental factors. It must have an effect on aging and longevity. I often talk about life attitudes that can be characterized by decades.

20-year-olds are fearless and have no concept of limits. Evel Knievel dare devils , Olympic athletes and Army recruits. 30-year-olds have a glimmer of age limits but it is fleeting.

40-year-olds begin to sense time is beginning to take its toll and are the most motivated and dedicated to achieving optimal health and well being. 50-year-olds are more aware of non-infinite mortality. 60 year olds sense the quickening of the sands of time.

70-year-olds are well aware of time limits. 80-year-olds are either highly motivated to passing the 90-year-old barrier or are totally accommodated to the facts of their own mortality. 80-year-olds are either marking time or actively engaged in longevity prolongation.

The Challenge for You

How do you characterize yourself? In what generation do you find yourself? In what decade do you find yourself? What are your goals and aspirations? What are your hopes and most fervent desires? What motivates you? These are vital questions at all ages but gather increasing importance with advancing age.

I hate the term senior citizen. It makes me want to blurt out, “right on, junior citizen.” My mother-in-law hates the term the Golden Years. So did my mother. They refer to it more often as the Rust Years not the Golden Years.

This dichotomy between Depression-era/WWII babies and Boomers needs more study and thought. It is today’s challenge to you. What do you want to do? We most definitely live in highly challenging times.

Epilogue

As Jerry Garcia said, “What a long strange trip it’s been.”

“It’s not the destination, it’s the journey”  – Ralph Waldo Emerson

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