In my daily reading of the latest scientific articles on longevity, I came across this terrific piece authored by leading researchers David Sinclair, Leonard Guarente, and Guido Kroemer. These are gentlemen I hold in high esteem in the anti-aging medicine field. I may not agree with all the ideas expressed, but I am on board with most. This article provides an overview of human clinical trials exploring various compounds and interventions that may have anti-aging effects.
It focuses on eight categories: Metformin, NAD+/sirtuins, GLP-1, Rapamycin, Spermidine, Senolytics, Probiotics, and Anti-inflammatories. For each category, the authors briefly explain the mechanism of action and then summarize completed and ongoing trials, assessing the current evidence for anti-aging effects in humans.
Overall, the article paints an optimistic view of life extension prospects while acknowledging the preliminary state of human data and the need for further research. The breadth of categories covered demonstrates the range of pathways being targeted to slow aging potentially. The authors conclude that the next few years may present a tipping point as the most viable approaches become evident and progress toward FDA approval for age-related diseases. Here is my summary of six breakthroughs they discuss:
1- Metformin
Metformin trials show evidence it may protect the heart, improve immunity, and reduce inflammation. Although I feel berberine is a better choice, some studies suggest that metformin may nullify some of the effects of exercise. Metformin and berberine are compounds that have become increasingly important in health and medicine. Metformin is a drug that has been used for decades to treat type 2 diabetes. It reduces glucose production in the liver, increases insulin sensitivity, and improves glucose uptake in tissues like fat and muscle.
Berberine is a compound found in some plants that seem to act very similarly to metformin. Studies have shown berberine also helps regulate blood sugar and insulin levels, making it potentially helpful in treating prediabetes and diabetes. Beyond effects on blood sugar, both metformin and berberine display other beneficial health effects:
They act as antioxidants, have anti-inflammatory effects in the body, improve gut health, and may even help extend lifespan. Both compounds mimic and augment our natural bodily processes related to metabolism and healthy functioning. The proven health benefits, general safety, and tolerance have made metformin a staple diabetes drug and berberine a useful over-the-counter supplement for overall wellness.
Metformin and berberine affect the AMP-activated protein kinase (AMPK) cellular signaling pathway, which is necessary because AMPK regulates metabolism and energy homeostasis. Specifically, metformin and berberine activate AMPK by inhibiting complex I of the mitochondrial respiratory chain. This increases the AMP/ATP ratio, mimicking a state of energy deficiency at the cellular level. The cell responds by activating AMPK, which functions as a master metabolic switch to stimulate catabolic, ATP-producing processes and inhibit anabolic, ATP-consuming processes.
Activation of AMPK has many beneficial downstream effects, such as increasing glucose uptake in skeletal muscles and fat while reducing glucose production in the liver and improving insulin sensitivity. AMPK will Increase fat oxidation and reduce fat storage while stimulating mitochondrial biogenesis and exerting anti-inflammatory effects.
By toggling this key AMPK switch, metformin and berberine exert cascading control over glucose and lipid metabolism, mitochondrial health, and more. Proper metabolic regulation is crucial for health, as diabetes and obesity are characterized by dampened AMPK signaling. Boosting AMPK activity with metformin or berberine helps restore metabolic balance. The multifactorial effects induced by AMPK activation make targeting this energy-sensing pathway an essential therapeutic strategy for managing metabolism.
2 – NAD+
NAD+ precursors like NMN and NR can reliably raise NAD+ levels, with evidence for cognitive and physical benefits. NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a vital role in many biological processes and promotes health as we age. NAD+ involves energy production, DNA repair, cell signaling, and metabolism regulation. Maintaining adequate levels of NAD+ as we get older can provide extensive health benefits.
Higher NAD+ levels allow cells to function correctly, reduce inflammation, and promote DNA repair. This helps delay the onset of age-related diseases. Sufficient NAD+ levels also increase mitochondrial function and stimulate sirtuins and other proteins in healthy aging. This is accomplished through better energy metabolism, increased mitochondrial function, reduced inflammation, improved DNA repair, and adequate NAD+ status, which supports overall vitality and longevity., maintaining adequate NAD+ levels supports optimal health and function into advanced age.
Overall, NAD+’s effects on sirtuins, AMPK signaling, circadian rhythms, DNA repair, and epigenetic modifications influence vital pathways that govern healthy cellular functioning and survival.
3 – Rapamycin
Rapamycin is a compound that has shown promising anti-aging effects in animal studies, including human studies. It works by inhibiting the mTOR protein pathway, which is involved in cell growth and proliferation. Inhibiting mTOR has increased lifespan and healthspan in various species. In some studies, treatment with rapamycin led to increased longevity, improved memory, reduced cancer risk, enhanced immunity, and better cardiovascular health.
Because rapamycin suppresses cell proliferation, rapamycin is already used to prevent organ transplant rejection. However, its ability to inhibit mTOR also produces anti-inflammatory, antioxidant, and metabolic benefits that slow aging. Rapamycin also enhances stress resilience, extends lifespan, reduces disease risk, and maintains vitality by modulating this critical protein pathway. This demonstrates rapamycin’s role as a life-extending therapeutic for aging humans.
4 – Spermidine
Spermidine is a compound that has emerged as a novel target for anti-aging therapies. It is a polyamine in foods like wheat germ, soybeans, and some fruits and vegetables. Consuming spermidine or increasing one’s internal production allows cells to maintain DNA integrity better and facilitate protein synthesis and degradation. These functions preserve youthfulness and boost health.
Higher spermidine intake is also associated with increased autophagy and longevity pathways like FOXO and mTOR. Through such regenerative and self-cleaning processes, spermidine supports healthy aging and longer lifespan. Studies in animals and human immune cells have confirmed these pro-longevity benefits. Spermidine’s cardioprotective, neuroregenerative, and anti-inflammatory properties also defend against cardiovascular disease, neurodegeneration, and cancer as we age. Supplementing spermidine late into life has reversed age-related dysfunction and disease in mice. So, while human trials are still expanding, raising spermidine levels through diet or supplementation promotes enhanced cellular function, stress defense, and renewed tissue homeostasis for healthier aging. I like to take this supplement daily.
5 – Senolytics
Cellular senescence refers to aged cells that have lost the ability to divide but remain biologically active. Senescent cells naturally accumulate as we age and are considered a fundamental contributor to the aging process and development of age-related diseases. While they have beneficial roles like wound healing and tumor suppression early in life, accumulating senescent cells later in life can compromise tissue structure and function. They also secrete numerous inflammatory, growth-promoting, and degrading substances into surrounding tissue. This activity, known as SASP (senescence-associated secretory phenotype), enhances chronic inflammation, impairs regular cell function, and alters tissue micro-environments in ways that promote cancer, diabetes, atherosclerosis, and more.
Removing senescent cells has been shown in animal models to alleviate multiple age-related diseases and improve healthspan. Human studies have shown the same thing. Research suggests managing their burden through immune system modulation, experimental senolytic drugs, or lifestyle tools like diet and exercise may support healthy aging. Harnessing the tools to regulate senescent cell activity shows immense promise for human health and longevity. Dealing with senescent cells has created a new field in medicine called
Senotherapeutics refers to a new class of medicines to treat the underlying biology of cell senescence. Some examples of senotherapeutic approaches include removing senescent cells, enhancing autophagy, modulating epigenetic alterations, and regulating cell signaling pathways related to aging. Early evidence suggests senotherapeutics may help strengthen resilience, restore function, improve healthspan, and extend lifespan. Animal models and some early human trials have demonstrated their ability to target molecular drivers of aging, alleviate frailty, enhance cognition, encourage tissue regeneration, and reduce risk for cancers, cardiovascular disease, osteoarthritis, Alzheimer’s, and more. The promise of Senotherapeutics alleviating the burden of age-related disability and disease, improving the quality of later life, and fundamentally treating aging makes them a fascinating prospect for the future of healthcare. Perhaps one of the most significant aspects of senescent cells deals with immunosenescence. This is the phenomenon where the cells of our immune system become senescent and begin to fail us. Failure of our immune system leads to many diseases.
6 – Anti-Inflammatories
Chronic inflammation is believed to be a significant driver of many age-related diseases. Finding ways to minimize inflammatory activity can, therefore, promote healthier aging. One of the most powerful inflammation regulators in the body is the NRF2 protein pathway. Activating NRF2 stimulates the production of antioxidant and detoxification enzymes that combat oxidative stress and inflammation at the cellular level.
A novel method for activating NRF2 is through a technique called EBO2, which stands for Extra Corporeal Blood Oxygenation and Ozonation. EBO2 molecularly stimulates the NRF2 network, ramping up endogenous antioxidant systems. Not only do we perform the EBO2 techniques at PUR-FORM, but we teach doctors all over the world this technique. Additional top inflammation fighters include omega-3 fatty acids like those found in fatty fish, which disrupt pro-inflammatory signaling; exercise, which helps release myokines with anti-inflammatory activity; and various polyphenol-rich foods like curcumin, resveratrol, and green tea, which attenuate neuroinflammation and inflammatory joint damage.
Anti-inflammatory nutrients like magnesium, vitamin C, vitamin D, zinc, and selenium also help control an overactive immune response. Employing a combination of techniques, including NRF2 activating techniques like EBO2, thus holds great potential for establishing an anti-inflammatory state and achieving healthy aging. What we are doing is decreasing Inflammaging.
The good news is that the previously mentioned regimens and other equally beneficial therapies are found at our PUR-FORM clinic. These would include EBO2, hyperbaric treatment, hydrogen therapy, and custom-designed IV therapies such as CoQ10, resveratrol, and phosphatidylcholine, which are available. What we do is combine these therapies in propriety manners. That makes all the difference. Remember, we don’t just practice anti-aging and regenerative medicine; we define it.
