The Department of Health and Human Services (HHS) and the FDA have conducted an in-depth review of the scientific evidence and have decided to remove the former “black box” warnings that had accompanied many hormone treatments since 2002.

For more than 20 years, those black boxes warned of a possible increased risk of heart attack, stroke, thrombosis, breast cancer, and dementia in all women using estrogen, regardless of age, timing of treatment initiation, or the type of hormone used. These warnings were largely based on early results from the well-known Women’s Health Initiative (WHI) study, conducted in women over 60 years of age, many with pre-existing cardiovascular disease, and using hormone preparations that are now largely obsolete.

Dr. Sánchez – Neolife Medical Team

What exactly has the HHS/FDA decided?

After reviewing decades of clinical studies and meta-analyses, the HHS concluded that these generalized warnings did not reflect current scientific knowledge and may have discouraged many women from receiving a treatment beneficial to their health.

The key changes include the removal of “black box” warnings from multiple systemic estrogen and estrogen–progestogen preparations. Package inserts still include warnings, but no longer as a global, alarmist message for all women. It is also stated that in women under 60 years of age or within 10 years of menopause, the overall evidence from clinical trials indicates that hormone therapy reduces coronary heart disease events and overall mortality, markedly lowers the risk of osteoporotic fractures, and may reduce cognitive decline and Alzheimer’s disease when initiated close to menopause (the so-called “window of opportunity”), although debate remains in this area. In addition, the FDA has created a dedicated expert panel on menopause and Menopausal Hormone Therapy (MHT) to update information for patients and healthcare professionals and to continue reviewing the evidence on an ongoing basis.

In summary, the official message has shifted from “avoid it unless absolutely necessary and for the shortest possible time” to “for many younger postmenopausal women, the benefits may clearly outweigh the risks when therapy is properly indicated and supervised.”

What evidence supports this new perspective?

As mentioned, the data review includes meta-analyses of clinical trials showing that women who start Menopausal Hormone Therapy before age 60 or within 10 years after menopause experience a 30% reduction in coronary heart disease and a 30–40% reduction in all-cause mortality compared with placebo. Trials in women with recent menopause (such as the Danish DOPS study and others) were also included, showing fewer cardiovascular events and fewer fractures in women treated with estrogen compared with untreated women. In addition, observational and neuroimaging studies were considered, suggesting a lower amyloid/tau burden or reduced dementia risk when therapy is initiated close to menopause, although results are not uniform and research is ongoing.

All of this has strengthened the “timing” or window-of-opportunity hypothesis: the effects of hormones depend greatly on when they are started (age and years since the last menstrual period) and on the type of estrogen and progestogen used.

It is also important to note that modern menopausal hormone therapy is based on the use of bioidentical hormones, primarily progesterone and estradiol, which are not equivalent to the synthetic hormones commonly referred to as progestins and estrogens that were also included in many of these studies. This distinction is critical, as many historical risks associated with hormone therapy stem from the use of progestins (such as Provera) or conjugated estrogens (such as Premarin), which are very different from the biological profile of molecules that the human body naturally produces or recognizes, such as bioidentical hormones.

The superiority of bioidentical hormones lies in the fact that the body recognizes them as its own, allowing them to exert specific effects on human receptors without significant off-target activation of unwanted pathways. In contrast, progestins and commercially available “progestogens” may also bind to androgenic or mineralocorticoid receptors, generating side effects.

Do risks still exist?

Yes, depending on the type of hormone, the route of administration, and the individual woman’s characteristics. Some hormones may increase the risk of venous thrombosis and stroke, particularly in older women, smokers, those with obesity, or those with pre-existing risk factors, and especially with high-dose oral estrogens.

Certain regimens combining estrogen with specific synthetic progestogens may slightly increase the risk of breast cancer after several years of continuous use. This is why choosing estradiol and progesterone in a balanced way, along with appropriate monitoring, is essential. The decision to treat a particular woman must remain individualized, taking into account personal and family history.

In fact, several experts have warned that enthusiasm for potential cardiovascular and neurological benefits should not be interpreted as a “free pass” to prescribe hormones to any woman. Consulting a healthcare professional who is experienced and up to date in this field remains essential.

What does this mean for you as a patient?

At Neolife, transparency and scientific rigor are central to how we share information with our patients, and we believe this update opens the door to more honest and nuanced conversations. If you are in perimenopause or within the first 10 years after menopause and experience bothersome symptoms (hot flashes, insomnia, vaginal dryness, mood changes) or have risk factors for osteoporosis, we can evaluate Menopausal Hormone Therapy not only as a symptomatic treatment but also as part of a long-term prevention strategy. Even if many years have passed since menopause, or if you have a history of thrombosis or hormone-dependent cancer, we will likely prioritize other treatment options, as the type of therapy (oral, transdermal, vaginal), dosage, and whether or not to combine with progesterone must be decided on a case-by-case basis after careful assessment.

Our approach at Neolife integrates these new recommendations with a thorough evaluation of personal and family history, as well as complementary studies. We favor bioidentical estradiol and micronized progesterone, which are the most extensively studied molecules and generally have the best safety profile. We also maintain close follow-up with each patient, with regular reviews to assess efficacy, potential side effects, and changes in risk factors, alongside lifestyle guidance.

In conclusion, the decision by the HHS and the FDA to remove the former “black box” warnings finally acknowledges what we at Neolife have long understood through continuous scientific updating: that current evidence paints a very different picture from that of 2002, and that when properly indicated and initiated at the right time, hormone therapy is a powerful tool not only for symptom relief but also for protecting bone and cardiovascular health in many women—adding more life to years.

If you are at this stage of life and have questions, we encourage you to reach out to us. The most important thing is to discuss it with a professional trained in hormone therapy, who can explain options, benefits, and risks transparently, and help you decide together what is best for you.

BIBLIOGRAPHY

(1) S. Department of Health and Human Services. (2024). HHS advances women’s health: Removes misleading FDA warnings on hormone replacement therapy. FDA Press Announcements

(2) Food and Drug Administration. (2025). FDA expert panel on menopause and hormone replacement therapy for women, 07/17/2025. FDA Expert Panels.

(3) Danish Osteoporosis Prevention Study (DOPS)

La entrada Hormone Therapy in Menopause se publicó primero en Neolife.

A 2020 study involving more than 800 men followed since 2004 revealed that testosterone therapy not only does not increase the risk of prostate cancer but that the detected cases are less aggressive and have a better prognosis.

The fear of prostate cancer should not automatically be a reason to deny testosterone replacement therapy in hypogonadal men, as long as proper monitoring protocols are followed and any underlying prostate disease is first ruled out.

Dr. Sánchez – Neolife Medical Team

What does the new study say?

A long-term follow-up of men with testosterone levels consistent with hypogonadism (testosterone of 350 ng/dL or 3.5 ng/mL) shows that testosterone therapy does not increase the incidence of prostate cancer — a risk historically attributed to this treatment — and, when it does occur, the tumors tend to be less aggressive than in men not receiving testosterone therapy.

What was studied and what were the findings?

A total of 428 men received testosterone therapy (T group) and 395 did not (control group, CTRL). The results are clear: only 2.8% of men treated with testosterone developed prostate cancer, compared with 11.1% in the untreated group.

Even more, in the testosterone-treated group, prostate cancer appeared only within the first 18 months of treatment, and most tumors were low grade (less aggressive). In contrast, in the untreated group, tumors tended to be more invasive and aggressive (higher Gleason scores).

Importantly, in the testosterone-treated group, no recurrences or prostate cancer–related deaths occurred, unlike the control group, where recurrences and 12 deaths were recorded during follow-up. Notably, almost all men treated with testosterone were able to resume therapy after surgery.

Conclusion: What are the implications?

Estos datos respaldan la seguridad de la terapia con testosterona en varones adecuadamente seleccionados que durante más de 30 años se ha ido demostrando (p.ej. el estudio TRAVERSE, ya comentado anteriormente en la newsletter de Julio 2024 ‘‘Cómo la TRHB puede reducir la mortalidad y el riesgo de padecer cáncer’’, disipando uno de los grandes temores en la práctica médica y abriendo la puerta a mejorar la calidad de vida de muchos hombres con seguridad y controles periódicos.

It turns out that testosterone not only appears to be safe, but may also be protective against the feared prostate cancer, as it is associated with less severe tumors when proper patient selection and follow-up are ensured.

Los estudios más recientes aportan tranquilidad: no existe una relación entre los niveles endógenos de Recent studies bring further reassurance: there is no link between endogenous testosterone levels and the development of prostate cancer. Moreover, exogenous testosterone therapy has not been shown to increase PSA levels or the risk of developing this type of cancer. In fact, contrary to what was once believed, high-grade prostate cancer has been associated with low testosterone levels in the blood (1).

To date, clinical studies have also confirmed that testosterone does not increase the risk of heart attack, and there is no evidence linking its use to a higher risk of prostate cancer—concerns that previously made physicians hesitant to prescribe this therapy. These findings align with the American Urological Association (AUA) recommendations, which since 2018 have stated that men undergoing testosterone therapy do not have a higher risk of developing prostate cancer—something these studies now strongly support.

The fear of prostate cancer should not automatically be a reason to deny testosterone replacement therapy in hypogonadal men, as long as proper monitoring protocols are followed and any hidden prostate disease is ruled out beforehand.

At Neolife, we consider it essential to inform patients that current evidence does not show an increased risk of prostate cancer associated with testosterone therapy in these contexts. We emphasize the importance of proper urological monitoring and individualized patient assessment in every case.

BIBLIOGRAPHY

(1) Raynaud, J.-P. (2009). Testosterone deficiency syndrome: Treatment and cancer risk. The Journal of Steroid Biochemistry and Molecular Biology , 114(1–2), 96–105.

(2) S. Haider, A. Haider, X. Xu, 376 Prostate Cancer (PCa) Incidence and Severity in 823 Hypogonadal Men With and Without Testosterone Therapy (TTh) in a Controlled, Observational Registry Implying 7,116 Patient-years, The Journal of Sexual Medicine, Volume 17, Issue Supplement_1, January 2020, Page S105, https://doi.org/10.1016/j.jsxm.2019.11.221

La entrada Testosterone and Prostate: Ally or Real Risk? se publicó primero en Neolife.

Melatonin has evolved from being considered merely the “sleep hormone” to a systemic modulator with significant effects on cardiovascular, metabolic, immune, and cognitive health. Recently, some controversy arose following the publication of preliminary observational data suggesting a possible association between long-term melatonin use and an increased risk of heart failure.

However, a critical review and detailed analysis of the information published by the American Heart Association (AHA) indicate that these types of studies do not establish a causal relationship and have important limitations. This is because they rely on large population databases and lack control over key factors such as dosage, duration of use, comorbidities, and participants’ sleep quality. These limitations reduce the clinical relevance of the findings, which should be interpreted as hypothesis-generating rather than definitive conclusions. For this reason, at Neolife we aim to share, with scientific rigor, the beneficial properties of melatonin beyond its role in regulating the circadian rhythm.

Dr. Sánchez – Neolife Medical Team

Beyond Sleep: A Key Molecule in Global Homeostasis

To date, no randomized clinical trials have confirmed any direct adverse effect of melatonin on the cardiovascular system. On the contrary, improving sleep quality—one of its main functions—helps reduce the risk of hypertension, diabetes, inflammation, and cardiovascular mortality.

What we do know about melatonin is that it shortens sleep latency and improves overall sleep quality, particularly in cases of sleep-onset insomnia. Moreover, it has a clear antioxidant effect and acts as an immune regulator with potential neuroprotective properties. And, importantly, it has a superior safety profile compared to benzodiazepines—melatonin does not cause dependence or cognitive impairment.

In recent years, melatonin has been found to play a fundamental role in maintaining the balance of the gut microbiome, opening up new therapeutic perspectives. It is now known that the gut contains concentrations of melatonin up to 400 times higher than those found in the brain. Melatonin is not only produced in the pineal gland but also in the gastrointestinal tract, where it acts locally on enteric receptors to modulate motility, immunity, and intestinal permeability.
This production occurs through intestinal bacteria, which can influence the conversion of tryptophan into serotonin—and subsequently into melatonin—directly affecting both its systemic production and function. This explains why patients with dysbiosis (an imbalance in the gut flora) often experience sleep disturbances, circadian rhythm alterations, and mood disorders.
Melatonin promotes the growth and maintenance of beneficial bacteria such as Lactobacillus and Bifidobacterium, while reducing pro-inflammatory species (LPS-producing bacteria), thus promoting a state of eubiosis (microbial balance). This activity helps reduce intestinal inflammation, improve mucosal integrity, and enhance immune response.

Melatonin is the only hormone with antioxidant properties, and its interaction with the microbiota reduces oxidative stress and inflammatory markers (TNF-alpha, IL-6), improving insulin sensitivity, lipid metabolism, and neuroendocrine regulation through the gut–brain axis.

Multiple studies suggest potential benefits of melatonin as an adjunct treatment in irritable bowel syndrome, stress- or antibiotic-induced dysbiosis, metabolic diseases (such as insulin resistance and obesity), and neurodegenerative disorders including Parkinson’s and Alzheimer’s.

Paradoxically, the same mechanisms that some observational studies have linked to cardiovascular harm are, in fact, those that protect the endothelium and reduce systemic inflammation, as supported by physiological evidence. Through its antioxidant action and its influence on the gut microbiome, melatonin reduces lipid peroxidation, enhances mitochondrial function (ATP production, i.e., energy), promotes a healthier lipid profile, regulates blood pressure and heart rate variability, and modulates the autonomic balance between the sympathetic and parasympathetic systems (vagal tone).

The bidirectional interaction between melatonin and the microbiome is emerging as an essential mechanism in the regulation of multiple physiological functions. Modulating this axis represents a promising therapeutic pathway in inflammatory, metabolic, and neurological disorders.

In this context, melatonin transcends its traditional role as a sleep regulator—it acts as a global modulator of the circadian–immune–microbial axis, with far-reaching effects on cardiovascular, metabolic, and neuroendocrine health.

Taken together, melatonin’s overall impact on the body is protective and homeostatic, especially when dosing and treatment are personalized by healthcare professionals.
At Neolife, the regulation of the circadian rhythm and quality sleep are considered fundamental pillars of treatment, with proven benefits for our patients’ well-being. We know that melatonin supplementation can help restore gut ecosystem balance (eubiosis) and serve as an adjunct therapy in conditions such as irritable bowel syndrome, stress-induced dysbiosis, and certain metabolic or neurodegenerative diseases.

The current clinical challenge lies in personalizing its use, adapting it to each individual’s age, chronotype, gut microbiome status, comorbidities, and clinical goals. While we await further research, current evidence supports a rational, safe, and medically supervised use of melatonin within a comprehensive, integrative approach to overall health and healthy longevity.

BIBLIOGRAPHY

(1) Iesanu, M. I., Zahiu, C. D. M., Dogaru, I.-A., Chitimus, D. M., Pircalabioru, G. G., Voiculescu, S. E., Isac, S., Galos, F., Pavel, B., O’Mahony, S. M., & Zagrean, A.-M. (2022). Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions. Antioxidants, 11(11), 2244. https://doi.org/10.3390/antiox11112244

(2) American Heart Association. Long-term use of melatonin supplements to support sleep may have negative health effects. News release, 3 Nov 2025.

La entrada Melatonin: from sleep to the gut-brain-heart axis se publicó primero en Neolife.

The genome, metabolome, and microbiome of a supercentenarian: clues for healthy aging.

At Neolife, we are always attentive to cutting-edge advances in aging science, and today we want to share a study that is generating significant interest. It is “The multiomics blueprint of the individual with the most extreme lifespan,” recently published in Cell Reports Medicine by Santos-Pujol and colleagues. This work deeply analyzes the multiple biological layers (genome, epigenome, transcriptome, metabolome, proteome, and microbiome) of a supercentenarian in an effort to understand how it is possible to age so extensively while maintaining exceptional health.

Dr. Sánchez – Neolife Medical Team

Study context

The individual analyzed (referred to as “M116” in the paper) was, at the time, the oldest person with verified longevity (117 years and 168 days), making her an exceptional case for studying the mechanisms underlying extreme lifespan.

The research team analyzed blood, saliva, urine, and stool samples, applying multiple omics techniques to compare her biological profile with that of older adults who were not supercentenarians.

One key conclusion is that extreme longevity does not occur simply by “avoiding” aging, but rather through an intriguing duality: clear markers of advanced age (e.g., very short telomeres) coexisting with protective mechanisms that appear to preserve health.

In other words: she had not “defeated” aging, but had managed it in an exceptional way.

Key findings relevant to anti-aging practice at Neolife

Below we summarize the most important discoveries that, from Neolife’s perspective, are relevant to our clinical vision and guidance.

1. Genomics and rare variants

Researchers identified approximately 3.8 million single nucleotide variants (SNVs) in the woman’s genome, of which about 91,666 were considered “variants of interest” (VOI) with potential effects on more than 25,000 genes. Among these, seven were homozygous and absent from the European control population. Notable genes affected included: DSCAML1 (immunity and cognition)
MAP4K3 (longevity regulation in model organisms)
TSPYL4 and NT5DC1 (lung function)
The PCDHA1-9 cluster (brain and heart health)

Functional enrichment analysis showed overrepresented pathways such as:
T-cell differentiation in the thymus
Response to bacteria
Antigen-receptor–mediated signaling
Other immune-related mechanisms
This highlights the potential importance of a robust immune system in healthy longevity.

An interesting observation: although her telomeres were extremely short (~8 kb on average and ~40% below the 20th percentile), she remained in good health. This suggests that telomere length functions more as a “chronological clock” than a direct predictor of disease. At Neolife, this reinforces the idea that aging biomarkers must always be interpreted in a broad clinical context.

2. Metabolomics and lipid/anti-inflammatory profile

She displayed a remarkably favorable lipid profile: extremely low VLDL cholesterol and triglycerides, and very high HDL cholesterol (“good cholesterol”). Likewise, she had many medium/large HDL particles and many large LDL particles, with low levels of small HDL particles — all pointing to very efficient lipoprotein maturation.

She also showed low levels of saturated fatty acids, esterified cholesterol, linoleic acid, and acetone (typically associated with poorer health), and high levels of free cholesterol, which have been linked to better prognosis.

Her inflammatory profile showed low concentrations of glycoproteins A and B, suggesting a reduced degree of systemic “inflamm-aging.”

Altogether, these findings support the clinical value of interventions aimed at:
Optimizing lipid metabolism
Controlling triglycerides
Improving lipoprotein particle composition
Reducing low-grade chronic inflammation
All areas that Neolife actively addresses in personalized programs.

3. Extracellular vesicle (EV) proteomics

The proteomic analysis of M116’s extracellular vesicles (compared to postmenopausal women aged 49–65) revealed 231 proteins with significant differences. Enriched functional groups included:
Coagulation
Immune system
Lipid metabolism
Apoptosis
Cellular detoxification
Cell adhesion
mRNA regulation

Notable patterns included increased lipid and cholesterol transport, enhanced lipoprotein remodeling and clearance, and greater oxidative stress response activity.

A surprising detail: the most overexpressed protein in M116 was SAA1 (serum amyloid A-1), typically associated with Alzheimer risk, although she showed no signs of neurodegeneration. This underscores the need to interpret proteomic elevations with nuance and within the individual’s full biological context.

4. Gut microbiome

M116’s gut microbiome displayed much greater diversity compared to control women aged 61–91, indicating an extraordinarily rich microbial ecosystem.

At the phylum level, Actinobacteriota were markedly elevated, especially the family Bifidobacteriaceae and genus Bifidobacterium, which normally decline with age—but here remained abundant.

In contrast, Proteobacteria and Verrucomicrobiota were decreased relative to controls, patterns typically linked to better health in advanced age.

Dietary records showed that M116 consumed about three yogurts per day containing Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, which support Bifidobacterium growth. Although causality is not proven, these findings open practical avenues worth exploring.

5. Epigenetics and “biological age”

Globally, M116’s estimated biological age (based on epigenetic methylation clocks) was significantly lower than her chronological age. For example, her “age pace” was −17.34 years, suggesting a slowing of epigenetic aging.

This confirms the value of incorporating epigenetic clocks into aging assessments, while acknowledging their limitations: epigenetics is modifiable, and the goal is to realign biological age toward younger values.

Implications for healthy aging practice at Neolife

This study matters deeply to us at Neolife, and here is what it teaches when translated into clinical practice:

Extreme longevity is not the result of a single miraculous intervention, but of a synergistic set of genetic, metabolic, immune, microbiological, and epigenetic mechanisms. At Neolife, we emphasize exactly this comprehensive approach.

Efficient lipid profiles, low inflammation, a favorable microbiome, and slowed epigenetic aging emerge as “health markers” rather than indicators of chronological age. For this reason, we promote a personalized strategy: thorough diagnostics, tailored interventions (nutrition, microbiota modulation, lifestyle optimization, lipid and epigenetic management), and continuous monitoring.

This case demonstrates something powerful: extreme longevity does not have to be accompanied by extreme disease. Some individuals can live over a century while maintaining functional, remarkably balanced biology.

Although the study examines a single subject —and therefore cannot be fully generalized— it offers valuable hypotheses applicable to individualized clinical programs:

• Assessing lipid metabolism beyond traditional cholesterol measures (lipoprotein profiling, HDL/LDL particle analysis)
• Monitoring low-grade inflammation (glycoproteins, EV markers)
• Analyzing the gut microbiome with special attention to Bifidobacterium and reduction of pro-inflammatory taxa
• Integrating genomics into longevity assessments, recognizing that there are no “magic genes,” but rather many variants whose effects accumulate and are modulated by lifestyle

This research reinforces the idea that age is an important factor but not an unavoidable destiny: aging and disease can be decoupled, as shown by this case. In the authors’ own words, “extreme age” does not necessarily equate to “poor health.”

For us, it emphasizes the importance of analyzing multiple layers of biology —inflammation, genetics, epigenetics, microbiome— all of which add up. And above all, it reminds us that there is no single formula for successful aging, but there are measurable patterns we can understand and, to some extent, modulate.

We believe this study by Santos-Pujol et al. opens the door to future interventions in epigenetics, microbiome modulation, and personalized prevention. And although much remains to be explored, it reinforces our daily mission at Neolife: to translate cutting-edge science into actionable strategies that help patients preserve —and even elevate— their quality of life as they age.

Our commitment at Neolife is precisely to translate these cutting-edge advances into practical strategies for our patients, helping them optimize their aging instead of resigning themselves to the passage of time.

If you would like to explore any of these biomarkers in more depth or understand how to incorporate them into your follow-up protocol, we would be delighted to assist you.

Thank you for joining us on this journey toward smarter, healthier aging.

BIBLIOGRAPHY

(1) Santos-Pujol, A., Matalonga, J., Calleja, N., Moratal, T., López-Montes, A., et al. (2025).
The multiomics blueprint of the individual with the most extreme lifespan.
Cell Reports Medicine, 6, 102368.
https://doi.org/10.1016/j.xcrm.2025.102368

La entrada Decoding the Secrets of Superlongevity: The Multi-Omics Map of the Longest Life in History se publicó primero en Neolife.

You’ve probably heard of medications like Ozempic, Wegovy, or Mounjaro, which are primarily used for weight loss or blood sugar control in people with diabetes.

But did you know that these therapies might be opening new doors in the field of longevity? We’d like to share how these small weekly injections can have powerful effects far beyond what was originally imagined…

Dr. Yéssica Sánchez – Neolife Medical Team

Less Inflammation, More Vitality, and… a Healthier Heart

Chronic inflammation—a silent process we often don’t notice but that progressively damages the body—is one of the main accelerators of aging. It’s involved in diseases like Alzheimer’s, certain cancers, and cardiovascular conditions.

Semaglutide, commercially known as Ozempic® or Wegovy®, not only supports weight loss but also significantly reduces inflammation. Studies have shown that it can lower inflammatory markers (like C-reactive protein, or CRP) by up to 43%, even beyond the weight-loss effect.

This anti-inflammatory action is especially enhanced by the reduction of visceral fat—the most dangerous type due to its strong link to cardiometabolic risk. For this reason, semaglutide is increasingly used in people who are overweight or obese, even if they are not diabetic, as part of a comprehensive strategy to improve metabolic health and reduce systemic inflammation.

Semaglutide has been shown to reduce vascular and cardiac inflammation, improving endothelial function, decreasing leukocyte (immune cell) adhesion, and lowering the expression of pro-inflammatory molecules like ICAM-1 and VCAM-1. It has also been associated with reduced myocardial inflammation, which may help reverse microvascular rarefaction (the loss of capillaries and arterioles that impairs microcirculation and is typical of metabolic syndrome).

All of this translates into less arterial stiffness, improved tissue perfusion (blood flow), and a reduced risk of cardiovascular events, such as heart attacks. Moreover, several studies have demonstrated that semaglutide lowers the incidence of major cardiovascular events (cardiovascular death, heart attack, or stroke) in people with obesity or type 2 diabetes.

Brain Protection

At the brain level, multiple studies suggest that these treatments may reduce the risk of cognitive decline and Alzheimer’s—even in people without diabetes. They are currently being investigated as potential allies in preserving memory and preventing age-related brain damage. This is largely due to their ability to reduce vascular inflammation and restore the integrity of the neurovascular unit.

In animal models, GLP-1 receptor agonists reduce amyloid plaques, neuroinflammation, and induce changes in microglia that promote a neuroprotective state. Additionally, observational clinical studies in people with diabetes show that semaglutide is associated with a 40–70% lower risk of being diagnosed with Alzheimer’s. In older individuals, GLP‑1 use is linked to lower incidence of 42 chronic diseases, including dementia.

One of the most interesting human studies in my opinion is a pooled analysis of seven clinical trials involving 1,094,761 patients (both men and women around 60 years old), selected from a U.S. patient database and followed for three years. The study cohort included 17,104 new semaglutide users and 1,077,657 new users of other antidiabetic medications. The efficacy of semaglutide was compared to each of the other antidiabetics studied.

Despite significant heterogeneity in insulin and semaglutide receptor profiles based on ethnicity, age, sex, obesity diagnosis, cardiovascular disease, and Alzheimer’s risk factors, these groups were balanced using propensity score matching. Patients with type 2 diabetes prescribed semaglutide had a significantly lower likelihood of being diagnosed with Alzheimer’s during a three-year follow-up visit compared to those prescribed other antidiabetic medications—regardless of sex, gender, or obesity status. In fact, the overall risk of a first Alzheimer’s diagnosis within three years was nearly double in the general elderly population.

Cellular Energy and Metabolism

These therapies optimize how our cells use energy, regulate insulin, and protect the mitochondria (the “powerhouses” of our cells)—all essential for slowing down aging from the inside by promoting a healthy metabolic environment.

So, Are They Just for Weight Loss?

Given all the points above, the answer is no. While they were initially introduced with that goal in mind, scientists are now studying them as potential anti-aging tools. In the future, they may become part of prevention programs targeting brain, cardiovascular, and metabolic health.

Should I Take Them?

Should I Take Them?
They’re not for everyone—but they may be worth considering for people with obesity, prediabetes, insulin resistance, or high cardiovascular risk. The decision should always be made together with a physician who can assess your case individually. At Neolife, we’d be happy to guide you and personalize this treatment to suit your needs.

BIBLIOGRAPHY

(1) Estato, V., Obadia, N., Chateaubriand, P.H. et al.Semaglutide restores astrocyte–vascular interactions and blood–brain barrier integrity in a model of diet-induced metabolic syndrome. Diabetol Metab Syndr 17, 2 (2025).

(2) William Wang, QuangQiu Wang, Xin Qi, et al. Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimer’s & Dementia. Vol.20, issue 12 (2024)

(3) Meca AD, Boboc IKS, Mititelu-Tartau L, Bogdan M. Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models. Curr Issues Mol Biol. 2024 Jun 13;46(6):5929-5949. doi: 10.3390/cimb46060354. PMID: 38921025; PMCID: PMC11202139.

(4) Guo X, Lei M, Zhao J, Wu M, Ren Z, Yang X, Ouyang C, Liu X, Liu C, Chen Q. Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats. Front Pharmacol. 2023 Aug 28;14:1146960. doi: 10.3389/fphar.2023.1146960. PMID: 37701028; PMCID: PMC10493299.

(5) Shayan Yaghmayee, Atefeh Sadat Moazzeni, Tannaz Jamialahmadi, Sercan Karav, Habib Yaribeygi, Prashant Kesharwani, Amirhossein Sahebkar, Neuroprotective and cognitive benefits of Semaglutide: Insights into the underlying molecular mechanisms, Neuroscience, Volume 579, 2025, Pages 187-197, ISSN 0306-4522

(6) Zheng, Z., Zong, Y., Ma, Y. et al.Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024).

(7) Wang, W., Wang, Q., Qi, X., et al.(2024) Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimer’s and Dementia 1-12.

(8) Papakonstantinou I, Tsioufis K, Katsi V. Spotlight on the Mechanism of Action of Semaglutide. Curr Issues Mol Biol. 2024 Dec 23;46(12):14514-14541. doi: 10.3390/cimb46120872. PMID: 39728000; PMCID: PMC11674233.

La entrada Small Doses, Big Effects: GLP-1 and Longevity se publicó primero en Neolife.

Aging is an inevitable biological process characterized by the progressive loss of cellular and physiological functions. This deterioration is the main risk factor for the development of chronic and degenerative diseases.

Although research on aging and age-related diseases is still in its early stages, recent years have seen significant advances in longevity studies. Notably, the increase in life expectancy and the prevalence of associated diseases make it urgent to develop effective preventive and therapeutic strategies. Today, researchers are faced with a major question: can we intervene externally to slow down the aging process?

Dr. Yessica Sánchez – Neolife Medical Team

Hallmarks of Aging

We’ve previously discussed the “Hallmarks of Aging.” In this article, we explore current advancements that directly address each of these hallmarks and attempt to answer the key question. Let’s examine the main mechanisms involved:

One of the most relevant processes is genomic instability, which arises when DNA repair systems stop functioning properly, allowing mutations to accumulate with significant functional consequences.

Another essential mechanism is telomere shortening—the structures that protect the ends of chromosomes. With each cell division, telomeres shorten until the cell loses its ability to replicate. It has been observed that activating the enzyme telomerase can slow this process in certain experimental models.

Epigenetic alterations also play a key role. Aging modifies gene expression without changing the DNA sequence itself, thereby affecting multiple cellular functions. These epigenetic changes are implicated in premature aging syndromes.

Proteostasis, or the maintenance of protein balance, is another pillar disrupted by aging. The body loses its ability to properly fold and recycle proteins, which leads to their accumulation. Diseases like Alzheimer’s are directly linked to this breakdown in protein quality control.

Alongside this is dysregulated nutrient sensing, in which cells lose sensitivity to key metabolic signals. It has been shown that a predominantly anabolic metabolism accelerates aging, while catabolic processes—promoted by practices such as fasting—favor longevity. In this area, compounds like rapamycin have demonstrated positive effects in animal models.

Mitochondrial dysfunction is another central factor. Mitochondria, responsible for cellular energy production, become less efficient with age, increasing the formation of reactive oxygen species and leading to progressive cellular damage.

Added to this is cellular senescence, a state in which cells stop dividing without dying. Although this initially serves as a defense against mutations, the accumulation of senescent cells contributes to inflammation and tissue deterioration.

Over time, there is also a decline in the number of functional stem cells, limiting the body’s capacity for regeneration. Lastly, altered intercellular communication, worsened by an inflammatory environment, undermines the coordinated function of tissues.

Strategies to Address Aging

Today, there are pharmacological, nutritional, and genetic strategies to target many of these aging processes. Even the gut microbiota plays a key role in regulating the immune system and thus is considered essential for longevity.

Of all available approaches, reducing chronic inflammation and eliminating senescent cells have drawn the most attention. Nutritional supplementation has also been recognized as important in preventing functional decline.

Research led by pioneering scientists like David Sinclair has shown that certain natural compounds can promote healthy aging. These compounds, known as caloric restriction mimetics, imitate the benefits of fasting by activating genetic pathways related to longevity.

These include spermidine, berberine, resveratrol, and quercetin. Trans-resveratrol and quercetin, for example, stimulate the activity of the SIRT1 gene, which is involved in DNA repair and other cellular processes that slow aging. Additionally, trans-resveratrol improves insulin sensitivity in a dose-dependent manner. Quercetin, a flavonoid with anti-inflammatory properties, primarily works by eliminating senescent cells, which are responsible for age-related degenerative processes.

A recent study by Murugesan et al. (2023) demonstrated that the combination of quercetin and trans-resveratrol significantly reduces fat deposits, further supporting their potential as a metabolic therapy.

Another important molecule is NAD⁺ (nicotinamide adenine dinucleotide), a coenzyme essential for energy metabolism and the activation of sirtuins. NAD⁺ production can be increased using precursors such as nicotinamide riboside or nicotinamide mononucleotides (NMN). However, at Neolife, we strongly recommend intravenous NAD⁺ therapy due to its superior effectiveness.

Spermidine also stands out for its ability to induce autophagy, a key process in cellular renewal that significantly impacts cell differentiation and maturation.

Lastly, berberine, a natural compound with mechanisms similar to metformin, activates the AMPK gene, regarded as a master regulator of metabolism. Its effects promote mitochondrial biogenesis, improve insulin sensitivity, and support blood glucose regulation.

Scientific Support for a Therapeutic Approach

A recent development in this field is the COSMOS study, presented in March 2025 during the American Heart Association’s scientific sessions. This randomized clinical trial assessed whether daily multivitamin supplementation could slow biological aging, as measured by DNA methylation-based epigenetic clocks.

The study included over 950 older adults (mean age: 70.2 years), who underwent blood testing at baseline, 12 months, and 24 months. In all five epigenetic clocks analyzed, the group receiving multivitamins showed a slower rate of biological aging compared to the placebo group. This effect corresponded to an approximate “deceleration” of four months in biological aging. The benefits were even greater in individuals with accelerated aging at the start of the study.

These findings add to the growing body of evidence, such as results from the Physicians’ Health Study II, which showed a reduction in the risk of invasive cancer with multivitamin use, as well as less age-related cognitive decline and memory loss.

Although further replication and clarification of mechanisms are still needed, studies like COSMOS, along with data from the Physicians’ Health Study II and USPSTF reviews, reinforce the idea that good nutrition and appropriate supplementation can be valuable allies in preventing age-related decline.

Healthy longevity is not the result of a single intervention but rather the integration of multiple factors: genetics, nutrition, lifestyle, metabolic health, hormonal balance, and inflammation control.

While supplements are not a substitute for a balanced diet or healthy lifestyle, they represent a valuable tool within a preventive approach and may help target key aging markers.

Thanks to science, we now have promising tools that allow us to intervene before disease appears. Among them, well-chosen supplements are gaining a more solid role. Studies like COSMOS open new doors to consider supplementation as a thoughtful, evidence-based component of longevity medicine.

BIBLIOGRAPHY

(1) Ni YQ, Liu YS, New Insights into the Roles and Mechanisms of Spermidine in Aging and Age – Related Diseases. Aging Dis. 2021 Dec 1;12(8):1948-1963.

(2) López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G, The hallmarks of aging, Cell. 2013 Jun 6;153(6):1194-217

(3) Sesso HD, Manson JE, Aragaki AK et al. COSMOS Research Group. Effect of cocoa flavanol supplmentation on preventing cardiovascular disease events: The COSMOS randomized clinical trial. Am J Clin Nutr. 2022; 115 (6): 1490-1500

(4) Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the prevention of cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012 Nov 14;308(18):1871-80. doi: 10.1001/jama.2012.14641. Erratum in: JAMA. 2014 Aug 6;312(5):560. PMID: 23162860; PMCID: PMC3517179.

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