What you need to know about AI, your future and your health

What you need to know about AI, your future and your health
Stephen Cherniske, MS

About the author: Stephen Cherniske is a biochemist specializing in healthy aging. He taught
Clinical Nutrition at two southern California universities, directed an FDA licensed clinical lab
for nutrition and immunology, and served on the faculty of the American College of Sports Medicine. Stephen helped to create the world’s largest medicinal plant library and pioneered the use of AI to develop plant-based therapeutics from that resource. He is a best-selling author with more than a million copies in print. In this essay he explores the potential of AI to improve health span (the number of healthy years we enjoy past 50). To gain the most from what is unfolding day by day in the world of AI, science and health,
subscribe to his blog at: STEPHEN’S BLOG 

The Pace of Change
If you’re paying attention to science news, you probably have a sense that we are entering a time of rapidly accelerating change. Importantly, all the changes you have seen in your life thus far have been increasingly better tools. You went from a flip phone to a smart phone because it was a better tool. And it was a choice you made to buy and use that tool. For most of you, AI is still a tool. Chat GPT helps you write a business proposal, Perplexity generates a research path for your
biology project, and every time you Google anything, an “AI overview” appears. Perhaps you’ve noticed that particular tool… that seemingly appeared out of nowhere, is rapidly evolving.

Fasten your seat belt. Because many scientists have already moved beyond the information gathering “tool” stage. We are using Shared Learning, in which AI becomes more like a research colleague. But no ordinary colleague; it’s one that immediately updates its algorithms and data sets to incorporate new information and expand our understanding of the world around us. I will demonstrate that activity here in a simple discussion with Perplexity. Keep in mind that this is just the beginning. See if you can pick out the limitations and biases that Perplexity employs; errors of omission that come from its human programmers. I believe that these errors will be eliminated as AI moves toward super-intelligence and independent operation. To put it simply, AI is no longer just a tool; it is becoming an active agent that will change our world in ways that are unpredictable. We are all about to be swept up in an accelerating level of change that will be daunting.

But you know what will not change? Your physiology. Your heart will still pump about 2,000 gallons of blood through 50,000 miles of blood vessels to nourish and detoxify 36 trillion cells. The question is, how will AI enhance, preserve or help restore your physiology? To answer that, I “interviewed” Perplexity, with a focus on longevity or healthy aging.

Stephen: Explore the ways that AI will advance and support healthy aging (health span).

Perplexity: Artificial Intelligence (AI) is transforming our understanding of the aging process and  opening the door to breakthroughs in treatments and technologies designed to enhance health span and lifespan. With the power to analyze massive datasets and identify patterns, AI is leading the charge in fields such as maintaining bone density and muscle mass, enhancing immune competence, and protecting the brain from dementia. Here’s how AI is driving innovation in these areas and shaping the future of aging research and treatment. 

PART 1. Maintaining Bone Density and Muscle Mass

Bone density and muscle mass naturally decline with age, increasing the risk of fractures, frailty, sarcopenia (age-related muscle loss) and Metabolic Syndrome. AI is playing a pivotal role in addressing these issues by: Predicting Osteoporosis Risk: AI algorithms can analyze medical imaging, genetic data, and lifestyle factors to predict the risk of osteoporosis and fractures.

Stephen: Would one early intervention be restoring youthful levels of DHEA (dehydroepiandrosterone)?

Perplexity: Yes. DHEA has been shown in multiple clinical trials, to increase bone mineral density (BMD) in women. Studies also show an increase in muscle mass in men and women, and fat loss in men supplemented with DHEA. Importantly, these benefits were greater when combined with weight-bearing exercise.

REFS: Clin Endocrinol (Oxf). 2018 Dec 9;90(2):293–300. doi: 10.1111/cen.13901. Sex- specific Effects of DHEA on Bone Mineral Density and Body Composition: A Pooled Analysis of Four Clinical Trials. Catherine M Jankowski, Pamela Wolfe, et al.

Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1003-8. doi: 10.1152/ajpendo.00100.2006. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Dennis T Villareal, John O Holloszy.

Optimizing Exercise and Nutrition Protocols: AI-driven personalized health programs can recommend specific exercise regimens and dietary interventions to maintain muscle mass and bone density. By using wearable devices and motion sensors, AI can assess the effectiveness of exercise routines and optimize them for individual needs, promoting strength and skeletal health.

Stephen: It seems like it would also be useful to include serum DHEA sulfate (DHEAS) in one’s annual blood chemistry, in order to stay in the optimal range.

Perplexity: The concept of “optimal” compared to the standard reference range has not been identified.

Stephen: I would argue that the reference range provided by the reporting lab, is meaningless, since it merely reflects the DHEAS level found in a reference population. For example, on my last blood test, the lab’s “normal” range went from 18 mcg/dL to 265 mcg/dL. How is it possible that one man could be “normal” at 18 mcg/dL and another man is also normal, with a DHEAS level fifteen times higher?

Perplexity: While the normal reference ranges for DHEA-sulfate (DHEAS) are indeed quite broad, determining an “optimal” level is more complex. Currently, there’s no universally agreed-upon optimal range in the medical community, as research is ongoing.

Stephen: Besides the studies showing benefits on bone density and muscle mass cited above, there are published reports on improvements in libido, mood and energy, associated with specific doses of DHEA. What more do we need to consider?

Perplexity:
1. There is a Plateau Effect: Research shows that increasing the dose of supplemental DHEA beyond 50 mg/day does not lead to a linear increase in serum DHEAS, which is good.

2. Physiological Levels: Some researchers suggest that maintaining DHEAS levels in the range typical of healthy young adults might be a useful target. 

Stephen: Please provide the best research to support that view.

Perplexity: Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHE Age Study to a sociobiomedical issue. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4279-84. Baulieu EE,Thomas G, Legrain, et al.

Stephen: To clarify, here is an excerpt from the conclusion of that study:

“The secretion and the blood levels of DHEA and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of DHEA to compensate for the decline counteracts defects associated with aging. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study.

No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a “young” concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical benefits here reported… A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging.”

Perplexity: The most appropriate approach is to work with a healthcare provider to interpret DHEAS levels in the context of an individual’s age, sex, overall health, and specific health goals.

Stephen: What else can we expect from AI?

Perplexity: Drug Development: AI is accelerating drug discovery by screening vast chemical libraries for compounds that can stimulate bone growth or slow bone loss. It can also model the molecular interactions of drugs with bone tissue, identifying promising candidates for clinical trials.

Stephen: DHEA has undergone extensive genomic and metabolomic analyses that reveal its precise molecular mode of action. In bone, DHEA is converted to estrone, which stimulates bone-building. At the same time, it down-regulates the genes that cause the breakdown of bone and connective tissue. DHEA increases muscle mass and improves strength by stimulating IGF-1, and by conversion to small amounts of testosterone. Best of all, it enhances the benefits of weight training, so that exercise produces measurable and visible results.

PART 2. Maintaining Immune Competence.

Perplexity: Aging is associated with a decline in immune function, leading to increased susceptibility to infections, autoimmune diseases, and cancer. AI is helping to maintain immune competence through:

Immune System Modeling: AI can simulate the complex interactions within the immune system, identifying how various factors like genetics, lifestyle, and environmental exposures influence immune aging.

Personalized Vaccination Strategies: As the immune system weakens with age, AI can help optimize vaccination schedules and formulations for older adults. By analyzing immune response data, it can predict the most effective vaccine types and dosages for different age groups, enhancing protection
against diseases like influenza, pneumonia, and even COVID-19.

Discovering Immunomodulatory Drugs: AI-driven drug discovery platforms can identify molecules that modulate the immune response to enhance its function in older adults. These could include drugs that reduce chronic inflammation, a key factor in age-related immune decline.

Stephen: What about DHEA?

Perplexity: In humans, DHEA synthesis peaks between age 20 and 30, declining thereafter at an accelerated rate. Since one of the consequences of this decline is failing immunity, it may be possible for AI to identify the physiological, genetic or biochemical cause of age- related DHEA decline, leading to the development of therapies to restore DHEA synthesis to youthful levels.

Stephen: But, as we have seen, maintaining youthful levels is already possible by supplementing with DHEA, monitoring blood levels of DHEA sulfate, and working with one’s primary care physician to optimize results. Please enumerate the ways that DHEA supports immunity.

Perplexity: DHEA (dehydroepiandrosterone) supports immunity through several mechanisms:

Enhancement of Immune Cell Function

1. T Cell Activation: DHEA stimulates the thymus gland, which produces T cells, a critical component of the adaptive immune system. This leads to an increase in T cell numbers and activity.

2. Natural Killer (NK) Cell Boost: DHEA supplementation has been shown to increase both NK cell numbers and cytotoxicity. In one study, NK cell numbers increased by 22-37%, with a 45% increase in cytotoxicity after 18-20 weeks of DHEA treatment.

3. B Cell Stimulation: DHEA can increase B cell populations and enhance their mitogenic response. One study found a 35% increase in B cells after 2 weeks and a 29% increase after 10 weeks of DHEA treatment.

Modulation of Cytokine Production

1. Interleukin-2 (IL-2) Production: DHEA has been shown to increase IL-2 production, which is crucial for T cell proliferation and differentiation. What’s more, increased IL-2 has been
shown to reduce the risk for autoimmune disease.

2. IL-6 Secretion: In vitro studies have demonstrated that DHEA can enhance mitogen-stimulated release of IL-6 by about 30%.

Stephen: That’s incredible. Is there a drug, available today or in development, that can have such a positive and comprehensive effect on immunity?

Perplexity: While DHEA has shown promising effects on immunity, there is no single drug that can replicate all of its benefits. However, some medications and compounds can provide similar immunomodulatory effects:

Thymosin alpha-1: This synthetic peptide stimulates T cell production and function, similar to DHEA’s effects on the thymus gland.

Stephen: When I last looked, TA-1 was going for about $250 per dose, and has to be injected by a physician

Perplexity: Interleukin-2 (IL-2): Available as a medication (aldesleukin), IL-2 enhances T cell and NK cell activity. It’s used in some cancer treatments and has shown potential in managing autoimmune conditions.

Stephen: Aldesleukin is a chemotherapy drug, administered via IV injection and has a laundry list of adverse side effects, many of which can be fatal.

Perplexity: Lenalidomide: An immunomodulatory drug that enhances T cell and NK cell function, used in treating certain cancers.

Stephen: This drug is available only under a restricted distribution program called the Lenalidomide REMS (Risk Evaluation and Mitigation Strategy) program.

Perplexity: It’s important to note that while these drugs may mimic some of DHEA’s immune effects, they don’t replicate its full spectrum of actions. DHEA has wide-ranging effects beyond just the immune system. Additionally, these medications have more specific targets and potentially more side effects than DHEA supplementation.

PART 3. Protecting the Brain

Perplexity: The most pressing challenge in aging research is protecting the brain from age- related decline and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. AI’s contributions in this field include:

Early Diagnosis of Dementia: AI algorithms can analyze brain imaging, cognitive testing, and even speech patterns to detect the early signs of dementia. This allows for earlier interventions to slow disease progression.

Drug Discovery for Neuroprotection: AI-driven platforms are identifying new compounds that can prevent or reduce the accumulation of toxic proteins like amyloid-beta and tau, which are linked to Alzheimer’s disease. By simulating molecular interactions, AI can expedite the search for neuroprotective drugs that can delay cognitive decline.

Neural Interface Technologies: AI is also playing a role in developing brain-computer interfaces and other neurotechnologies that can assist people with neurodegenerative diseases

Stephen: Early detection and future drug development does not sound very exciting.Please review the known benefits of DHEA for neuroprotection and regeneration.

Perplexity: Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) have demonstrated several neuroprotective and regenerative effects in the brain and nervous system. Importantly, the brain synthesizes DHEA specifically for  protection and the activation of neuronal stem cells.

Neuroprotective Effects

DHEA exhibits neuroprotective properties in various experimental models:

• Protection against glutamate excitotoxicity 13
• Reduction of neuronal death in ischemia models 35
• Attenuation of damage from traumatic brain injury and spinal cord injury 35
• Amelioration of neurodegenerative disease processes 3

The mechanisms underlying these neuroprotective effects include:

• Antioxidant properties 13
• Anti-inflammatory actions 13
• Antagonism of glucocorticoid effects 4
• Enhancement of BDNF (brain-derived neurotrophic factor) expression 5

Neuroregenerative Effects

DHEA promotes neuroregeneration and plasticity:

• Stimulation of neurite growth 14
• Enhancement of neuronal survival 4
• Promotion of myelination 5
• Upregulation of growth-associated protein 43 (GAP-43), which is necessary for axonal regeneration 5
• Activation of neuronal stem cells for repair and regeneration.

Neurobiological Actions

At the cellular and molecular level, DHEA exerts several beneficial effects:

• Modulation of neurotransmitter systems, including GABA and NMDA receptors 24
• Enhancement of neuroplasticity 2
• Regulation of neuronal energy metabolism 5

Effects on Brain Function

DHEA and DHEAS administration has been associated with improvements in:

• Memory and cognitive function24
• Mood regulation2
• Reduction of anxiety and depressive symptoms24

Therapeutic Potential

Given these neuroprotective and neuroregenerative properties, DHEA has shown promise as a potential therapeutic agent for various neurological conditions, including:

• Neurodegenerative diseases like Alzheimer’s and Parkinson’s 34
• Mood disorders 24
• Anxiety disorders 2
• Traumatic brain injury and spinal cord injury 35

It’s important to note that while these findings are promising, much of the research has been conducted in preclinical models or small clinical studies. Further research is needed to fully elucidate the mechanisms of action and potential therapeutic applications of DHEA in neurological disorders. What’s more, one cannot assume that all the benefits and actions listed above will be achieved by oral supplementation with DHEA tablets, capsules or topical creams.

Stephen’s SUMMARY

By now, you have seen that Perplexity has a strong bias towards the drug-oriented approach to healthy aging. When prompted, however, it was able to bring up, explain and summarize research on DHEA. Thus, our job as AI users, will be to increase the number of queries regarding natural vs
drug-oriented information. In the Shared Learning model, your

AI device will start to incorporate more and more information related to your particular interest.

Bottom Line: In the three main areas identified by Perplexity as ways in which AI will facilitate healthy aging, virtually every future “advance” is already here. DHEA has been available in the US since the 1994 Dietary Supplement Health and Education Act (DSHEA) classified it as a nutritional supplement (since it can be derived from a plant; the Mexican yam.)

And that is part of the hangup, since conventional doctors are taught that natural products are worthless or even dangerous. The main objection you are likely to hear from your doctor is that DHEA can “mess with your hormones.” Let’s explore that, first in regards to your brain.

As we learned, DHEA is synthesized in the brain. In fact, it is considered to be the most important neurosteroid. DHEA levels in the brain and body begin to decline around age 30. By age 70, levels are approximately 10 to 15% of what one produced at age 20. This decline corresponds precisely with cognitive decline, and brain imaging studies have shown a positive benefit from supplementation.

REF; Sripada, R., Marx, C., King, A. et al. DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli. Neuropsychopharmacol 38, 1798–1807 (2013). https://doi.org/10.1038/npp.2013.7

The concluding paragraph of nearly all DHEA investigations include the statement that “more [larger, longer] studies need to be conducted.” This is the poison statement that essentially stops the information going from research (no matter how compelling) to its clinical application in the doctor’s office. In the not-so distant past, a guiding principle for doctors was the risk/ reward ratio. Without years-long, double blind, placebo controlled clinical trials with thousands of subjects, doctors looked at the evidence at hand and compared the observed benefit to the potential risks. Anyone who reviews the available and ongoing research with DHEA must conclude that the
benefits far outweigh the risks, considering that studies have been specifically designed to explore this.

There are more than adequate human clinical trials including multi-year studies with hundreds of volunteers. Read the conclusion of one of these studies published in the Journal of Clinical Endocrinology and Metabolism. This is a human study with a 25 mg / day group and a 50 mg / day group.

“No accumulation of steroids was observed. No worrying transformation to androgen and estrogen was recorded; indeed, the limited increased estradiol in aged women could be predicted to be beneficial. These results suggest that daily oral administration of DHEA (25/50 mg) is safe in elderly subjects. The 50-mg dose was chosen for a 1 yr, double blind, placebo-controlled trial of daily oral administration of DHEA in 60- to 80-yr-old individuals.”

REF: Legrain S, Massien C, Lahlou N, Roger M, Debuire B, Diquet B, Chatellier G, Azizi M, Faucounau V, Porchet H, Forette F, Baulieu EE. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab 2000 Sep;85(9):3208-17.

Another study, conducted by the Mayo Clinic, looked at 144 men and women over two years. They used high doses (75 mg/d for men and 50 mg/d for women), looking for any adverse effects on blood chemistry, prostate, breast, uterus or endometrium. Compared to placebo, no adverse effects were
observed.

REF: Nair KS, Rizza RA, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006 Oct 19;355(16):1647-59.

To review:

1. As a natural hormone produced by the body, DHEA cannot be patented. Thus no billion dollar profits, no deep training in medical school (not even in endocrinology), no post- graduate seminars (nearly all funded by drug companies) and a conspiracy of silence that continues to this day. I know that’s a lot to take in. If you discuss this with your conventional doctor, be prepared to hear them say that DHEA is risky because it can raise systemic levels of sex steroids (testosterone and estrogen). This is false; a canard; a smokescreen to get away from a topic on which they are ill-informed.

2. We know that conversion of DHEA to sex steroids takes place only in tissues with high repair needs (eg brain, bones), on an as-needed basis, through an inherent self-regulating activity. I’m going to say this again. The repair and regenerate benefits of DHEA come from local (or peripheral) anabolic activity such as was recently demonstrated in the journal, Mechanisms of Ageing and Development. This important study utilized genomic technology to reveal that DHEA improves bone density, not by raising systemic levels of estradiol, but through local conversion to estrone by osteoblasts. Again, DHEA is converted by repair cells in the bone to estrone… which is perfectly safe, while leaving estradiol levels in the breast and uterus unchanged.

REF: Takayanagi R, et al. DHEA as a possible source for estrogen formation in bone cells: correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1.25- dihydroxyvitamin D3 in human osteoblasts.” Mech Ageing Dev 2002; 123:1107-14.

3. You can monitor your DHEA level with a simple blood test. Tell (do not ask) your doctor to include serum DHEA Sulfate (DHEAS) in your annual blood chemistry. You can also have this tested without the need of a doctor’s requisition. Here are two easy-to-use options.

* https://www.lifeextension.com/lab-testing/hormones
* https://www.anylabtestnow.com/

Note 1: Your goal is to stay in the optimum range. For women, you’re looking for a DHEAS level from 200 to 350 mcg/dL. For men, optimum DHEAS is 350 to 500 mcg/dL.

Note 2: Do not take any DHEA for 12 hours before the blood draw.

Note 3: If you are a man being treated for prostate cancer, or a woman being treated for breast cancer, you need to discuss DHEA supplementation with your oncologist.

Note 4: DHEA is not a magic bullet. Diet and lifestyle are critical co-factors, but it is reasonable to say that no diet, supplement program or exercise will effectively increase your
healthspan if your DHEA levels are plummeting.

And finally, is there an optimal DHEA formulation?

Natalie and I created Synergized DHEA for Men and Synergized DHEA for Women, based on the latest
research showing remarkable benefits from DIM (diindolylmethane) and alpha lipoic acid. The Women’s
formula also provides Chaste Tree Berry extract. Details on these companion ingredients can be found here: https://my2048.com/alpha-lipoic-acid-ala/

And now… coming soon to a pharmacy near you…

This was predictable, right? There are now three new drugs: synthetic derivatives of DHEA, in development. We have no idea if they will be more effective than natural DHEA, but you can be sure of three things: They will be patentable, expensive and carry new side effect risks.

BNN 27 is being developed for neuroprotection
Triplex for immune stimulation
Fluasterone: Anti-inflammatory, antioxidant and immunity

Onward!