A “natural” process, due to progressive aberration of hormone balance

AGING

In the words of our modern prophet, whose name is “AI”, “Aging is a natural process of gradual change that occurs over time, with declining physical and mental capacity, and an increased risk of disease and death” ……

Otherwise put, (according to the Merck manual, in a chapter by Richard G. Stefanacci, DO, MGH, MBA, of Thomas Jefferson University, Reviewed/Revised in Apr 2024), “Aging is a gradual, continuous process of natural change that begins in early adulthood.”

However that estimate was based on history, not biology: what our gurus have thus far failed to realise is that aging is due to progressive reduction of essential hormone manufacture and is preventable.

“Older adult” status can be defined variously:

Chronologic age

Chronological age helps to predict many health problems, but has limited significance in terms of health, since mainly, it is reduced health, rather than normal aging, that causes functional loss with advancing age.

Biologic, or Physiologic, age 

Biological, or physiological, age refers to bodily changes which occur with aging:
the timing of changes is variable, but some people are biologically old at 65, others not until later. However, many of the noticeable differences in biological age among people of similar chronologic age are caused by lifestyle, habit and subtle effects of disease, rather than by differences in actual aging.

Psychological age

Our estimate of psychological age is based on affect, mood, social interactions and responsiveness to physical psychological and cognitive stimuli: an 80-year-old who is humorous, learns quickly, works, plans, anticipates future events, and participates in (youthful) activities is considered psychologically younger.

“Pure Aging”

“Pure aging” refers to changes, such as thickening and stiffening of the lenses in the eyes (presbyopia), forgetfulness, reduced efficiency of glucose metabolism, mild reduction in learning facility and/or general cognition, reduced muscle mass, muscle strength and joint flexibility, increased sensitivity to cold due to arteriosclerosis, that occur in the absence of “disease”.

The rate of aging

In the absence of “disease”, the rate at which an individual ages varies markedly, the factors being genetics, presence or absence of deleterious habits, level of physical activity throughout life and the degree of life stress to which he or she is subject.

“Id-perceived” Stress

Stress, as recognised and evaluated by the hypothalamus, which receives information from all our senses and sensors, is variable.

The hypothalamus rates the threat level of input from the sensors as it relates to the person’s physical and cognitive preparedness for the current situation: thus, a threatening situation is viewed by the hypothalamus as “tolerable”, or “stressful”, depending on the individual’s inherited traits, physical fitness, mental preparedness, previous experience, social and financial stability, family coherence and support, personality, self-image and cognitive ability.

If the hypothalamus perceives that a current stressor represents a significant threat, it instantly secretes ACTH (Adreno-Cortico-Trophic Hormone), which instructs the adrenal glands to secrete cortisol, the “stress hormone”.

Cortisol (1) reduces DHEA and Pregnanolone production by the adrenal glands and (2) prevents intracellular conversion of T4 (thyroid 4) into T3, causing T3 deficiency.

Therefore, in situations of chronic stress, the rate of objectively-observed age change increases, because T3 deficiency is a major cause of hair loss, depigmentation of the hair, dry skin, hoarseness, constipation and anxiety, while pregnenolone deficiency, by reducing progesterone and Allopregnanolone production, results in poor sleep, mood alteration, depression and reduced pain control.

Studying Aging

Gerontology is the study of the aging process, including physical, mental, and social changes, with the intent to develop strategies and programs for improving the lives of older adults.
Geriatrics is the branch of medicine that specializes in the care of older adults, which often involves managing many disorders and problems at the same time.

Normal aging, from an internal, subjective standpoint

People often wonder whether what they are experiencing as they age is normal or abnormal. Although people age differently, some changes result from aging itself: such changes are considered normal, “pure” aging effects, which occur inevitably and are to be expected. For example, in virtually all humans, beginning in the 5^th decade, the lens of the eye thickens, stiffens, and eventually is unable to focus on close objects. This disorder, presbyopia, often followed by development of cataracts, is considered normal aging. On the other hand loss of joint mobility, with difficulty in bending to retrieve a foreign object, is blamed on “aging”, but is actually due to failure to maintain mobility by exercise.

Healthy (successful) aging

Healthy aging refers to postponement of, or reduction in, the undesired effects of aging: it is achieved by maintenance of exercise and cognitive activity. The goals of healthy aging are maintaining physical and mental health, avoiding disorders and illnesses, and remaining active and independent.

Healthy habits can help – habits such as
·       Following a nutritious diet
·       Avoiding cigarette smoking and excessive alcohol use
·       Exercising regularly
·       Staying mentally active by means of games, social engagement, work or study.

Improve your habits ASAP

It seems, taking the United States as a prime exemplar, that  healthy aging is on the rise, although the maximum life expectancy has remained unchanged.
Recent reports from the USA indicate
·       A decrease in the percentage of people over age 65 with debilitating disorders,
·       A decrease in the percentage of people aged 75 to 84 who report impairments,
·       An increase in the numbers of the oldest old – people age 85 and older,

The sooner you develop good habits, the better: it is never too late to begin!

Other factors affecting healthy aging

Heredity: Heredity influences whether a person will develop a disorder. For example, a person who inherits genes that increase the risk of high cholesterol levels is likely to have a shorter life, while one who inherits genes protective against coronary artery disease and cancer is likely to have a longer life. There is good evidence that living to a very old age – to 100 or older – runs in families.

Lifestyle: Avoiding smoking, not abusing illicit drugs and alcohol, maintaining a healthy weight and diet, exercising, and getting recommended screening examinations help people function well and avoid disorders.

Exposure to toxins (here, “toxins” include heavy-metal overloads): such exposure can shorten life expectancy even among people with the best genetic makeup.

Health care: Preventing disorders, or treating them after they are contracted, especially when the disease can be cured (as with infections and sometimes cancer), helps increase life expectancy. In fact, the life expectancy of Americans has been increasing dramatically over the past century, although the maximum lifespan is unchanged. A male child born in 1900 could expect to live only 46 years, and a female, 48 years, while in 2021, the average life expectancy in the United States for the total population was 76 years.

Although much of this gain can be attributed to a decrease in childhood mortality, life expectancy at every age beyond 40 has also increased dramatically. For example, a 65-year-old man can now expect to live to about age 83, and a 65-year-old woman, to about age 86.

Overall, women live about 4 to 5 years longer than men, a difference in life expectancy which has changed little, despite late 20th-century and early 21st-century changes in women’s lifestyle, including experiencing more stress.

What factors are involved in aging – do our scientists really know?

According to the Max Planck Institute, “It is widely accepted that damage to genetic material, cells and tissues, which accumulates with age and cannot be repaired by the body, is the cause of the loss of function associated with aging. What is less clear is what causes this damage at the molecular level and why it can be repaired in young organisms but not in old ones.”

……… As an earlier generation of British comedians used to say, “Therein, lies the rub!”

In brief, much is written and many theories have been proposed:

· Every aspect of our changing physiology and biochemistry associated with “aging” has been claimed, by “this authority” or “that”, to be an active, causative factor in the process: viz.
“Genomic instability”,
“Epigenetic changes”,
“Loss of Proteostasis”,
“Impaired 1^st space perception of nutrients”,
“Mitochondrial dysfunction”,
“Cellular senescence”,
“Exhaustion of stem cells”,
“Altered intercellular communication”,
“Chronic inflammation”,
“ Imbalance of the intestinal flora” ……. Etc.
However, in scientific claims, authors often confuse “cause” with “effect”.

·  Virtually every variable, from stress with elevated cortisol, to chronic inflammation, to poor sleep habits, nicotine, alcohol or recreational drug habituation, menopause, mitochondrial dysfunction, cellular senescence, UV radiation, air pollution, reduced telomere length, sugar, fast food and even facial expressions, has been written up as a target for elimination by means of changes in lifestyle, diet, particular exercise, vegetable and mineral supplements.

·  Amazing, Miraculous, Modern Drugs, from which Big Pharma hopes to Make Big Bucks, are (Lord, Help Us!) in the works: for example, “RAPAMYCIN improves immune function through End Lysosomes, protecting against an increase in pro-inflammatory factors with age”……

Rapamycin is considered a promising antiaging drug, which improves health in old age and alleviates the age-related decline in immune function, in fruit flies. A research group of the Max Planck Inst. for biology of aging has discovered that in fruit flies, rapamycin activates the (so-called) “end lysosomes”, which have a similar function to the stomach in our cells……..

Rapamycin is used in cancer therapy and after organ transplants and has been found to extend the lifespan and health span of laboratory animals. It extends lifespan via 2 mechanisms: increased autophagy and decreased activity of a protein called S6 K.
Mice with Rapamycin-altered S6 K live longer: “Altered activity of S6 K influences the end lysosomes, which break down material in the cells and play an important part in regulating various cellular processes such as inflammation”.

The mechanism by which Rapamycin acts is unclear, but “the flies live longer, show better immune function in old age and are able to clear bacterial infections more efficiently”.

Okay, okay: enough of that!

It’s going to take a couple of decades for our Magical Pharmaceutical Companies to come up with a “drug” which can solve the problem of aging: this presents a difficulty for you and me, who are aging, as we speak.

So let’s talk some sense: let’s have a look at what we actually know, for sure, about humans:

Aging, from the standpoint of a functional & metabolic medicine/hormone balancing professional

Humans were designed to live healthy lives for 25 years and thereafter, to give up the ghost so that someone else can have enough potatoes and lentils.

Without delving into the intricacies of metabolic function, senescence, telomeres, and various enzyme processes, and without considering the use of magic drugs such as rapamycin, there are a few things that we can say, with assurance:

Assuming that we were born healthy, delivered without difficulty by an unstressed, fit and happy mother, and assuming that our life remains unstressed through our ‘teens, plus the first half of our third decade, our aging process begins at approximately 18 – 20 years of age, with the demise of our putative “diurnal timer” (the pineal gland).

The demise of the pineal gland

At the end of our 2^nd decade, our pineal gland inexplicably atrophies and calcifies, replacing itself with calcium salts which resemble dental enamel (the hardest material in our bodies).

The decline of DHEA and Pregnenolone

The graphic below is by dePerretti and Forrest (1976): it shows the serum DHEA trends of human and other long-lived vertebrates and compares the incidence of human non-communicable diseases (red line) with other long-lived vertebrates (Dotted red line). It also proposes that with DHEA supplementation, the solid red line can be made to parallel the dotted one.

Figure 2: Effect of DHEA loss, and the promise of supplementation, re. liability to cancer: from J.W. Nyce, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106910/    It shows the age-related diminution of DHEA production, and the “promise” that maintaining a maximal level would prevent noncommunicable diseases, e.g. cancer.

NOTE:

Serum levels of Pregnenolone follow a curve similar to that for DHEA

At 25 years of age, just as we fulfil our destiny, our production of Pregnenolone and DHEA, the raw materials from which our all-important “neurosteroid” hormones is manufactured, begins to fall. It is progressively reduced, by 1–2% per annum, so that by age 80–90, our adrenal glands have ceased manufacturing the hormones, leaving our brains as the only source of these two all-important “Neurosteroid Hormone” precursors.

DHEA supply

For adequate hormonal function, the serum DHEA needs to be 6 µmol (micro moles) per litre, or more. If it is less, cortisol begins to rise, the cortisol suppresses T3 formation and the end result is the beginning of intracellular hypothyroidism.

The young male’s DHEA production exceeds the female’s by 40 or 50%, yielding a serum level of 11 – 14 µmol per litre, as compared with the female upper limit of 10 – 11 (or so).
Therefore in spite of the yearly 1% loss, men keep their DHEA serum level over 5 µmol per litre through age 40 – 50.
But in the female, who starts with a high of 11 µmol/L, the serum level falls below 6 µmol/L by age 35–40 years if she is lucky – if she is not, she becomes DHEA deficient by age 25, with resultant increase in cortisol production, followed by reduction in T3 formation from T4. Thus she joins the ranks of young women with low-grade hypothyroid symptoms, including dry skin, hair loss, brittle fingernails, constipation, anxiety, poor sleep and “brain fog”.

Pregnenolone supply

17-hydroxypregnenolone reaches its maximum level at the age of 18 – 20 years. In men, it falls to its minimum by age 39, while in women, it is minimised by age 37. pregnenolone is essential to the production of progesterone and thus, Allopregnanolone, so a deficiency of Pregnenolone leads to all the problems associated with insufficient Allopregnanolone

Estrogen supply

The male maintains his serum  estrogen by “aromatization” of testosterone; but in the female, the ovaries, through the effect of some life process which we do not understand, discontinue the manufacture of eggs, estradiol and progesterone, somewhere between the age of 35 and (more usually) 45 – 50. This sets the stage for bone loss, with osteopenia, and eventually, osteoporosis.

Testosterone supply

In the female, the Testosterone level depends on the supply of DHEA, which is often inadequate by the 2^nd decade: serum testosterone, which is “normally” 20 – 30 pmol per litre, will be low (and at times, zero) in the 3^rd decade, if DHEA production has been compromised by severe psychological stress: stress-related hypercortisolemia reduces DHEA production and I have seen 25-year-old females with zero testosterone.

In the male, Testosterone is only rarely deficient in the 2^nd and 3^rd decades, but when DHEA manufacture is reduced, the serum Testosterone is often at the lower limit of normal: one of my patients, a 19-year-old who presented with sexual dysfunction, had a serum Testosterone below the lower limit of normal.

T3, the functioning thyroid hormone

In both males and females, serum T3 becomes deficient in the presence of stress-related hypercortisolemia, because Cortisol blocks the conversion of T4 to T3 within the cells (intracellular hypothyroidism). In these cases, serum reverse T3 (rT3) is elevated because cortisol also “up regulates” the conversion of T4 into rT3: the condition is diagnosed if the T3/rT 3 ratio is less than 20.

So: never mind the pontifications of those who profess to an understanding of the minutiae of biochemistry, aberrations of enzymatic function, reduction of telomere length following cell division, altered activity of 50 6K, rapamycin etc, etc., etc.!

The important questions, and the important answers

The answers to the questions, “why do we age” and “how do we age” are:

(1) We age because we are designed to shut down hormone production gradually, beginning at age 25.

(2) We age by progressively reducing the efficiency of all cellular systems, because the hormones which promote efficient cellular function all fall slowly, from their peaks in the 2^nd and 3^rd decades of life, each to a minimum which is inadequate to maintain the intracellular processes necessary to efficiency and vigour.

Okay! Now that we know how and why, let’s approach the question “What can we do to slow aging?”.

How can we can slow the “aging” process?

·       Stress triggers an inflammatory response in the body, cancels the all-important, efficiency-promoting effect of T3 and reduces DHEA and Pregnenolone production, thereby laying the groundwork for consequent hormonal aberrations and accelerated deterioration of all our systems. To begin with therefore, our best efforts should be made to minimize stress and its effects from the beginning of pregnancy, through childhood and the teen years.

·       Since children often experience stress in circumstances which seem perfectly normal to their parents, observation of hormone levels should begin in childhood, or at the latest, puberty and should be repeated periodically throughout life, with the proviso that hormone restoration therapy be applied promptly, to correct hormonal deficiencies, ad hoc.

·       Bioidentical hormone restoration, based on periodical reassessment of serum levels, should be continued throughout life, so as to ensure that the body has the “tools” to maintain normal cellular function.

·       Judicious selection of supplementary nutrients such as NAC, I3C, Vitamin D, Resveratrol, Magnesium etc. should be taught in schools and the entire population should be educated regarding the effects of and remedies for, hormone imbalance.                   

·       Other deleterious factors, such as poor diet, substandard hygiene, inadequate exercise, toxins such as nicotine, alcohol and recreational drugs, poor sleep habits, excessive UV radiation, EMF exposure, risky contact with infective agents, heavy metal contamination etc. should be avoided.

·       Amicable and supportive social contacts should be maintained.

·       Equitable, egalitarian but non-permissive social structure, including modern amenities, just taxation, universal education, support for disabilities and other functions of government should be optimised.

Are these goals achievable? And assuming that they are, won’t it take 60 years to prove?

A protocol of hormone, vitamin and mineral observation and ad hoc support should ideally begin at, or before, conception and should be continued for one’s lifetime: as such, proving its efficacy would be a matter of a 100-year-long study. We might however make some headway in our learning curve by observation over a shorter period of time, beginning at a later age and stage of life: a study of perhaps 20 years, beginning at age 65, might show some effects supporting the premise that hormonal and metabolic support might reduce the rate of aging.

I’m sure that other metabolic medicine/hormone balancing professionals must have “cases”, whose experience could be added to mine, but currently, I have only one such subject: myself!

My own BIHRT

I began the hormonal support journey at the age of 67 and am now aged 85: my weight is stable, at 170 pounds and my height is 5’9” (originally 5’10 1/2”). Based on my original height, my BMI is 24.0. My blood pressure is usually 130/70 and my pulse, 72–80.

I am active: I attend two “stretch” classes per week and play pickle ball regularly. My kidney function is “borderline”, but I have no other disabilities and T3 is my only prescribed medication.

I have lost muscle strength, but not muscle mass.

Perhaps the best demonstration of the benefits of hormone balancing is my own record of aging and perhaps the best method of demonstrating my physical changes with age is a pictorial presentation.

With this in mind, I present hereunder, a series of photographs of myself, beginning in 1998. I will leave it to the reader to decide whether, or not, my personal hormone protocol has been effective.

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