In my biochemistry classes, I learned a lot about cellular biology. For example, I learned about genetics, and I learned about a large variety of intracellular processes orchestrated by weird-sounding proteins.
Unfortunately, for the most part, my professors failed to mention that we are not solitary single-celled organisms but rather a collection of billions of intricately interdependent cells that cooperate for a common goal (i.e., to pass on my genes effectively to the next generation).
To ensure proper cooperation of these individual cells, early animals evolved a large number of signaling molecules to instruct each other on how to behave under certain conditions in order to serve the greater good (i.e., the survival and reproduction of the organism).
If these molecules are used for sending signals between cells over long distances (e.g., in vertebrates via the bloodstream) these molecules are called “hormones”, which derives from ancient Greek and means “to set in motion”.
For about 500 Mio. years, hormones have been coordinating the behavior of individual cells throughout the animal kingdom. In vertebrates, there are a vast number of different hormones, each for a distinct purpose. Some of these hormones act at the most powerful layer of intervention – namely, to alter the expression of genes directly.
Hormones are not everything, but without proper hormonal health, everything is nothing. Unfortunately, hormone replacement is a very neglected area in the conventional healthcare system.
I discuss some of the most important hormones, and my experience with them, here.
Hormones & aging
As I age, hormone levels decline across the board and my cells are progressively deprived of these crucial intercellular mediators.
While the age-related hormonal decline is “natural”, evolution never prepared humans to be much older than age of 40. The hormonal decline is simply a byproduct of the aging process, including a deterioration of the hypothalamus, pituitary gland, peripheral glands, and target cells. In my opinion, restoring hormones to youthful levels is just as unnatural as living beyond the age of 50 anyway.
Proper hormone levels are crucial for graceful aging. Hormones are needed to help with nutrient partitioning, energy generation, musculoskeletal health, brain function, heart health, and pretty much everything my body does. Furthermore, hormones are intricately linked to vitality.
To me, longevity means much more than simply maximizing my lifespan. Above all else, it means maximizing my quality of life. If I had to choose, I would choose vitality over lifespan any day. In my opinion, achieving excellent health, performance, and well-being beyond the age of 50 is hardly possible without the use of at least some exogenous hormonal support – at least for most people.
- First, hormones are important for maintaining the structure and function of all of the tissues and organs in my body.
- Second, hormones have a major say in how I feel, which then co-determines the lifestyle choices I make.
Hormones & lifespan
I will now briefly discuss various hormones and how they relate to different aspects of the aging process. This list is far from exhaustive.
Cortisol
An aquiantance of mine who used high doses of hydrocortisone (25mg/d) noticed his hair greying. After stopping the hydrocortisone, the greying reversed again.
Cortisol is a steroid hormone that co-regulates about 20% of the genome. The primary purpose of cortisol is to prepare the mind and body for action and stress.
The amount of cortisol someone produces is one of the many variables determining how fast someone ages. At high levels, cortisol has pro-aging effects on every cell of the body because cortisol downregulates the expression of a number of genes involved in cellular repair, anabolism, and autophagy.
There are two closely related species of opossums with almost the exact same genetic makeup. However, one species has a 20% longer lifespan than the other (under laboratory conditions). It turns out, that the faster-aging species evolved to have substantially higher levels of cortisol because it lives in a much more dangerous habitat (predation) and it is thought that the higher levels of cortisol partially explain the faster rate of aging.
Higher levels of cortisol may also be part of the reason why some females seem to have aged five or more years over the course of a single pregnancy, a time during which cortisol levels are double to quadruple their normal levels. Speculatively, cortisol may also be part of the reason why the body of 39-year-old MLKJ reportedly looked like the body of a 70-year-old during autopsy. Due to the intense pressure he was under, his adrenals have probably been secreting vast amounts of cortisol for many years.
There is a reason for the saying that “stress can kill you”. Well, it is not the “stress”, but rather the associated hypercortisolemia.
Thyroid hormones
Thyroid hormone’s primary role is to increase the metabolic rate of every cell in the body. In simple terms, thyroid hormones make everything faster. For example, this includes the rate at which nutrients are metabolized, neurons communicate, hairs grow, or wounds heal. All else being equal, thyroid hormones also increase the speed of aging, and there are correlations between having lower levels of thyroid hormones and being a centenarian.
However, things are more complex than this. Thyroid hormones are highly anti-atherogenic. Furthermore, thyroid hormones stimulate the immune system and also reduce the risk of neurodegeneration. Moreover, higher thyroid hormones are correlated with greater vitality, which then affects lifestyle choices, which then affect the aging process.
In sum, while higher thyroid hormones may decrease maximum lifespan, higher thyroid hormones may have a protective effect against some usual causes of death, and thyroid hormones may also increase health span.
Growth hormone & IGF-1
Growth hormone & IGF-1 are in some respects similar to thyroid hormones in terms of lifespan & health span. By stimulating the ras-PI3K-mTOR pathway, GH & IGF-1 may decrease maximum lifespan.
Daf2 gene knockout (IGF-1 receptor) in C. elegans increases lifespan by almost 100%. Increased activity of the ras-PI3K-mTOR pathway may also be the major reason why larger dogs have shorter lifespans than smaller dogs. Furthermore, higher levels of GH & IGF-1 or insulin are associated with a greater incidence of cancer.
However, higher levels of IGF-1 are also associated with better metabolic health, less atherosclerosis, cardioprotection, better kidney health, better joint and bone health, greater muscle mass, and less dementia. Furthermore, GH and IGF-1 have potent effects on energy levels, mood, well-being, cognition, vigor, and vitality. All of these affect the lifestyle choices we make…and around 80% of us will be killed by diseases that are tightly linked to lifestyle.
When it comes to the “ideal” IGF-1 levels, good things seem to happen at both ends of the U-shaped curve. An IGF-1 towards the lower end disinhibits autophagy and stem cell proliferation. An IGF-1 towards the higher end stimulates tissue maintenance, repair, and growth. Thus, instead of aiming for IGF-1 levels that are constantly low (like while fasting) or constantly high (like when taking GH), the best approach is presumably to cycle IGF-1 levels from low to high.
Tactics: My current approach to hormone replacement
Tweaking my hormones has taught me how much my mood & functioning are co-determined by my hormone levels at any given point in time. I discuss some of my experiences with hormones in more detail here.
Currently, I supplement with a low dose of metreleptin and I am on my TRT Lite protocol.
My IGF-1 is still fairly high and I will consider using 1IU of growth hormone in a couple of years from now.
Strategies I follow to optimize my hormones naturally
- I optimize my sleep.
- I make sure I eat enough calories (about 3500-4000kcal per day), with enough good carbs and good fats. Whenever my caloric intake is insufficient, some of my hormones decline, including sex hormones, thyroid hormones, and IGF-1.
- I stopped any kind of fasting (both multi-day fasting as well as intermittent fasting) in part because fasting can cause all sorts of hormonal issues.
- I put a prime on exercise – but I make sure not to overdo it.
- I used to make sure that I do not dip below 14% body fat. Whenever I did, a number of hormones took a hit. Starting semaglutide allowed me to tolerate about 2% lower levels of body fat without hormonal deterioration but I am currently off it. I now circumvent this problem altogether by taking a low dose of metreleptin sufficient to mimic a body fat percentage of about 15-20% (but without the aesthetic and metabolic downsides). Furthermore, leptin has many great metabolic effects, particularly if insulin sensitivity is high at the same time.
- I take a couple of supplements to prevent nutrient deficiencies (discussed here).
- I run an extensive hormone panel once per quarter (discuss here).
I discuss my personal experience with hormones in more detail here.
My Longevity Protocol (Long & Technical Version)
This article is part of a much larger post describing my complete longevity blueprint. For my full protocol, read here.
Sources & further information
- Scientific article: The physiology of endocrine systems with ageing
- Podcast: Peter Attia – The endocrine system: exploring thyroid, adrenal, and sex hormones
- Opinion article: Dr. Linder – Hormones
Disclaimer
The content on this website represents the opinion and personal experience of the author and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without a doctor’s supervision. The content presented is exclusively for informational and entertainment purposes. Never disregard professional medical advice or delay in seeking it because of something you have read on the internet.