Introduction Intermittent fasting Cold exposure therapy Nutrigenomics and supplements Regulating circadian rhythms for longevity Neuroplasticity and cognitive health The longevity blueprint: Key takeaways What if you could slow down aging, optimize your body’s performance, and extend your lifespan — all through scientifically-backed lifestyle modifications? Biohacking, an emerging and revolutionary approach to human enhancement, offers just that. ​​​​​​​Image Credit: Girts Ragelis/Shutterstock.com Introduction Biohacking has surged in popularity as a means to optimize health and extend lifespan, blending scientific advancements with a do-it-yourself ethos. At its core, biohacking encompasses a wide range of strategies, from lifestyle modifications to cutting-edge biotechnology.1 While some methods, like optimizing diet, exercise, and sleep, have strong scientific backing, more experimental approaches, such as implantable technologies and genetic self-modification, raise ethical and safety concerns.1 One scientifically supported biohacking strategy is the use of wearable biosensors to track physiological data, allowing individuals to fine-tune their health in real-time.1 Additionally, dietary interventions such as intermittent fasting and ketogenic diets have been shown to enhance metabolic health and promote longevity by influencing cellular pathways like autophagy and insulin sensitivity.2 Supplementing with nootropics or compounds that may improve cognitive function is another avenue under investigation, with some substances like caffeine and omega-3 fatty acids demonstrating benefits.3 However, more extreme biohacking methods, including self-experimentation with gene editing or unregulated supplements, lack robust scientific validation and pose significant risks. Additionally, the use of implantable technologies, where individuals insert Radio Frequency Identification and Near Field Communication chips, biosensors, or magnets into their bodies to interact with electronic devices or augment their senses have raised significant ethical concerns.1 As biohacking continues to evolve, distinguishing evidence-based strategies from speculative or hazardous practices remains essential for its responsible application.1 This article explores five evidence-based biohacking strategies with the potential to promote longevity. The Rise of Postbiotics for Gut Health Intermittent fasting Intermittent fasting involves cycling between periods of eating and fasting, promoting metabolic adaptation. Research suggests that intermittent fasting enhances longevity by triggering autophagy, reducing oxidative stress, and improving insulin sensitivity.4 A key mechanism behind these benefits is the metabolic switch from glucose to ketone-based energy, which has been linked to improved mitochondrial function and reduced inflammation.5 Studies indicate that intermittent fasting may lower the risk of metabolic disorders, cardiovascular diseases, and neurodegenerative conditions.2 Additionally, intermittent fasting has been shown to modulate gut microbiota, which plays a crucial role in immune function, inflammation, and overall health.5 Furthermore, emerging research suggests that intermittent fasting can also influence gene expression related to longevity by activating sirtuins, a family of proteins involved in cellular repair and aging.4 However, the long-term implications of different intermittent fasting protocols remain an area of active research, necessitating further clinical trials to establish optimal fasting durations for longevity benefits. Despite its benefits, intermittent fasting is not suitable for everyone. Individuals with certain metabolic disorders, pregnant women, or those with a history of eating disorders should consult a medical professional before attempting fasting regimens.2 Future studies should focus on personalized approaches, considering factors such as genetic predisposition, lifestyle, and existing health conditions. Cold exposure therapy Cold exposure, including practices such as ice baths and cryotherapy, induces hormesis — a biological phenomenon where mild stressors elicit adaptive benefits. Exposure to cold also activates brown adipose tissue (BAT), leading to enhanced thermogenesis and metabolic efficiency.6 Moreover, research suggests that cold exposure modulates immune function, reducing inflammation and neuroinflammation.7 This effect may be particularly relevant for aging, as chronic low-grade inflammation is a key driver of age-related diseases. In addition to reducing inflammation, cold exposure has been linked to increased norepinephrine levels, which contribute to improved mood, cognitive function, and stress resilience.7,8 Some studies suggest that regular exposure to cold temperatures may even enhance cardiovascular health by improving vascular function and circulation.8 However, excessive cold exposure can be harmful, leading to hypothermia or increased cardiovascular strain in individuals with pre-existing health conditions.8 It is essential to adopt a gradual approach, starting with brief cold showers or localized ice application before progressing to more extreme methods such as ice baths. Further research is essential to determine the ideal duration and frequency of cold exposure to maximize longevity benefits while minimizing potential risks. Download your PDF copy now! Nutrigenomics and supplements Nutrigenomics explores the relationship between genes, diet, and health, allowing for personalized nutritional interventions. Certain compounds, such as nicotinamide mononucleotide and resveratrol, have been studied for their potential role in enhancing cellular energy production and lifespan extension. Nicotinamide mononucleotide supplementation has been shown to boost the levels of nicotinamide adenine dinucleotide (NAD+), a coenzyme critical for mitochondrial function and cellular repair, which declines with age.9 Similarly, resveratrol, a polyphenol found in red wine, has been linked to the activation of sirtuins, proteins associated with lifespan extension in various organisms.10 Polyphenols such as quercetin and curcumin have also been studied for their anti-inflammatory and antioxidant properties, which may contribute to healthy aging. Recent advancements in microbiome research have also highlighted the role of gut bacteria in metabolizing nutrients and influencing health outcomes. Probiotics and prebiotics may enhance gut health, promoting better nutrient absorption and immune function. Additionally, omega-3 fatty acids, vitamin D, and magnesium are emerging as key nutrients in longevity science, with studies linking them to reduced risks of chronic diseases.10,3 While nutrigenomics shows promise, supplementation should be tailored to individual needs. Overuse of certain compounds can lead to adverse effects, and more research is needed to establish optimal dosages and long-term safety. Is The Carnivore Diet Healthy? Regulating circadian rhythms for longevity Quality sleep is a crucial determinant of longevity, with evidence linking disrupted sleep patterns to increased risks of cardiovascular disease, cognitive decline, and metabolic disorders.11 Melatonin, a hormone that regulates circadian rhythms, plays a key role in sleep quality and longevity. Maintaining a consistent sleep schedule and minimizing exposure to artificial light at night can improve sleep quality and support healthy aging. Aligning lifestyle habits with natural circadian rhythms, such as enhancing exposure to natural light to increase melatonin production, may also promote optimal hormonal balance and metabolic efficiency.12 In addition to melatonin, sleep hygiene practices such as reducing caffeine intake, optimizing the bedroom environment, and engaging in relaxation techniques before bed contribute to better sleep quality. Poor sleep has been associated with increased levels of beta-amyloid, a protein linked to neurodegenerative diseases such as Alzheimer’s disease.12 Moreover, emerging research suggests that deep sleep plays a crucial role in metabolic regulation, immune function, and brain detoxification. Future studies should also explore the interplay between sleep and longevity, identifying potential interventions to enhance sleep efficiency and mitigate age-related decline. Neuroplasticity and cognitive health Cognitive decline is a major challenge in aging populations. Strategies to enhance neuroplasticity — such as meditation, brain-training exercises, and nootropic compounds — have been extensively investigated for their potential to slow cognitive aging and improve mental resilience.3 Meditation has also been shown to reduce stress-related neuroinflammation, while studies have reported that certain nootropics, such as caffeine, may enhance cognitive function. Regular physical exercise, particularly aerobic and resistance training, has been associated with increased neurogenesis and improved brain health.3 Technological advancements in neurofeedback and brain-computer interfaces may further enhance cognitive longevity. Current studies are striving to identify the most effective cognitive enhancement strategies while balancing efficacy with ethical considerations and safety. The longevity blueprint: Key takeaways Biohacking presents a promising avenue for longevity optimization, but it requires a critical and evidence-based approach. While intermittent fasting, cold exposure, nutrigenomics, sleep optimization, and neuroplasticity interventions show scientific merit, their long-term implications need further exploration. The current understanding suggests that future research should focus on refining these strategies and personalizing interventions to maximize their benefits while minimizing risks. Adopting a holistic, scientifically validated approach to biohacking may provide a sustainable pathway to extended health span and improved quality of life. References Yetisen A. K. (2018). Biohacking. Trends in Biotechnology, 36(8), 744–747. https://doi.org/10.1016/j.tibtech.2018.02.011 Reddy, B. L., Reddy, V. S., & Saier, M. H., Jr (2024). Health Benefits of Intermittent Fasting. Microbial Physiology, 34(1), 142–152. https://doi.org/10.1159/000540068 Dresler, M., Sandberg, A., Bublitz, C., Ohla, K., Trenado, C., Mroczko-Wąsowicz, A., Kühn, S., & Repantis, D. (2019). Hacking the Brain: Dimensions of Cognitive Enhancement. ACS Chemical Neuroscience, 10(3), 1137–1148. https://doi.org/10.1021/acschemneuro.8b00571 Anton, S. D., Moehl, K., Donahoo, W. T., Marosi, K., Lee, S. A., Mainous, A. G., 3rd, Leeuwenburgh, C., & Mattson, M. P. (2018). Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity, 26(2), 254–268. https://doi.org/10.1002/oby.22065 Patterson, R. E., Laughlin, G. A., LaCroix, A. Z., Hartman, S. J., Natarajan, L., Senger, C. M., Martínez, M. E., Villaseñor, A., Sears, D. D., Marinac, C. R., & Gallo, L. C. (2015). Intermittent Fasting and Human Metabolic Health. Journal of the Academy of Nutrition and Dietetics, 115(8), 1203–1212. https://doi.org/10.1016/j.jand.2015.02.018 Bujarrabal, A., & Schumacher, B. (2016). Hormesis running hot and cold. Cell Cycle, 15(24), 3335–3336. https://doi.org/10.1080/15384101.2016.1235859 Spiljar, M., Steinbach, K., Rigo, D., Suárez-Zamorano, N., Wagner, I., Hadadi, N., Vincenti, I., Page, N., Klimek, B., Rochat, M. A., Kreutzfeldt, M., Chevalier, C., Stojanović, O., Bejuy, O., Colin, D., Mack, M., Cansever, D., Greter, M., Merkler, D., & Trajkovski, M. (2021). Cold exposure protects from neuroinflammation through immunologic reprogramming. Cell Metabolism, 33(11), 2231–2246.e8. https://doi.org/10.1016/j.cmet.2021.10.002 Esperland, D., de Weerd, L., & Mercer, J. B. (2022). Health effects of voluntary exposure to cold water - a continuing subject of debate. International Journal of Circumpolar Health, 81(1), 2111789. https://doi.org/10.1080/22423982.2022.2111789 Bai, L. B., Yau, L. F., Tong, T. T., Chan, W. H., Zhang, W., & Jiang, Z. H. (2022). Improvement of tissue-specific distribution and biotransformation potential of nicotinamide mononucleotide in combination with ginsenosides or resveratrol. Pharmacology Research & Perspectives, 10(4), e00986. https://doi.org/10.1002/prp2.986 Kussmann, M., & Fay, L. B. (2008). Nutrigenomics and personalized nutrition: science and concept. Personalized Medicine, 5(5), 447–455. https://doi.org/10.2217/17410541.5.5.447 Zisapel N. (2018). New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. British Journal of Pharmacology, 175(16), 3190–3199. https://doi.org/10.1111/bph.14116 Espie, C. A. (2022). The ‘5 principles’ of good sleep health. Journal of Sleep Research, 31, e13502. https://doi.org/10.1111/jsr.13502 Further Reading

Flying with a food allergy can be daunting. I receive so many messages from my followers asking about flying and which airlines to choose when you have allergies. I’ve decided to write this blog post to give you a better understanding of my process and hopefully help you manage it better! Preparing for Your Flight It’s important to research the airline’s allergy policies beforehand. Every airline has its own policies regarding allergies, so it's always best to know ahead of time. It can be super frustrating and scary when the airline industry doesn't take your allergy seriously. It's definitely worth taking some time to pick an airline with a good track record, although this can be hard because everyone can have different experiences with the same airline. Some airlines have changed their policies and no longer serve nuts on flights. This is a massive step forward and a relief for so many people who fly regularly. We can only hope that more airlines follow in their footsteps! It’s also always worthwhile getting a letter from your doctor saying that you have an allergy and carry medication for it.

When it comes to managing food allergies, most of us focus on knowledge. We research symptoms, memorize allergen lists, and practice using an epinephrine injector in controlled scenarios. But what happens when knowledge collides with fear in a moment that demands action? That’s the question I faced during a recent experience with my oldest daughter, and the answer was humbling. Alarming Signs of a Reaction On that afternoon, my daughter – who has multiple food allergies – began showing alarming signs of a potential anaphylactic reaction after eating a small bowl of dry Honey Nut Cheerios. She started with excessive, uncontrollable coughing, followed by difficulty breathing, shortness of breath, and a sense of lethargy that sent my heart racing. As I stood there watching her struggle, I was consumed by fear. My daughter’s allergies include eggs, dairy, nuts, shellfish, cinnamon, and strawberries. Thankfully, she had recently passed her wheat challenge, and under her allergist’s guidance, we’d reintroduced wheat into her diet. In all her years of managing these allergies, we’ve been fortunate – she had never experienced a severe reaction requiring an epinephrine pen. But as I watched her symptoms escalate, I knew this might be the moment we had always prepared for.

Mammograms, with the help of artificial intelligence (AI) models, may reveal much more than cancer, according to a study being presented at the American College of Cardiology's Annual Scientific Session (ACC.25). The findings highlight how these important cancer screening tools can also be used to assess the amount of calcium buildup in the arteries within breast tissue—an indicator of cardiovascular health. The U.S. Centers for Disease Control and Prevention recommends that middle-aged and older women get a mammogram—an X-ray of the breast—to screen for breast cancer every one or two years. About 40 million mammograms are performed in the United States each year. While breast artery calcifications can be seen on the resulting images, radiologists do not typically quantify or report this information to women or their clinicians. The new study, which used an AI image analysis technique not previously used on mammograms, demonstrates how AI can help fill this gap by automatically analyzing breast arterial calcification and translating the results into a cardiovascular risk score. We see an opportunity for women to get screened for cancer and also additionally get a cardiovascular screen from their mammograms. Our study showed that breast arterial calcification is a good predictor for cardiovascular disease, especially in patients younger than age 60. If we are able to screen and identify these patients early, we can refer them to a cardiologist for further risk assessment." Theo Dapamede, MD, PhD, postdoctoral fellow at Emory University in Atlanta and study's lead author Heart disease is the leading cause of death in the United States but remains underdiagnosed in women and there is also lagging awareness. Researchers said the use of AI-enabled mammogram screening tools could help identify more women with early signs of cardiovascular disease by taking better advantage of screening tests that many women routinely receive. A buildup of calcium in blood vessels is a sign of cardiovascular damage associated with early-stage heart disease or aging. Previous studies have shown that women with calcium buildup in the arteries face a 51% higher risk of heart disease and stroke. To develop the screening tool used for this study, researchers trained a deep-learning AI model to segment calcified vessels in mammogram images—which appear as bright pixels on X-rays—and calculate the future risk of cardiovascular events based on data obtained from the electronic health record data. The segmentation approach is what separates this model from previous AI models developed for analyzing breast artery calcifications. Researchers said the model is also strengthened by its use of a large dataset for training and testing, which included images and health records from over 56,000 patients who had a mammogram at Emory Healthcare between 2013 and 2020 and had at least five years of follow-up electronic health records data. "Advances in deep learning and AI have made it much more feasible to extract and use more information from images to inform opportunistic screening," Dapamede said. Overall findings showed the new model performed well at characterizing patients' cardiovascular risk as low, moderate or severe based on mammogram images. After calculating the risk of dying from any cause or suffering an acute heart attack, stroke or heart failure at two years and five years, the model showed that the rate of these serious cardiovascular events increased with breast arterial calcification level in two of the three age categories assessed—women younger than age 60 and age 60-80, but not in those over age 80. This makes the tool particularly well suited for providing early warning of heart disease risk in younger women, who can benefit more from early interventions, researchers said. The results also showed that women with the highest level of breast arterial calcification (above 40 mm2) had a significantly lower five-year rate of event-free survival than those with the lowest level (below 10 mm2). For example, 86.4% of those with the highest breast arterial calcification survived for five years compared with 95.3% of those with the lowest level of calcification. This translates to approximately 2.8 times the risk of death within five years in patients with severe breast arterial calcification compared to those with little to no breast arterial calcification. The AI model was developed as a collaboration between Emory Healthcare and Mayo Clinic and is not currently available for use. If it passes external validation and gains approval from the U.S. Food and Drug Administration, researchers said the tool could be made commercially available for other health care systems to incorporate into routine mammogram processing and follow-up care. The researchers also plan to explore how similar AI models could be used for assessing biomarkers for other conditions, such as peripheral artery disease and kidney disease, that might be extracted from mammograms.

Women of childbearing age who had both ovaries removed, in a procedure called bilateral oophorectomy, were more likely to develop heart failure later in life, according to a study being presented at the American College of Cardiology's Annual Scientific Session (ACC.25). Bilateral oophorectomy is often recommended to treat and, in some cases, prevent certain health issues, including endometriosis, pelvic inflammatory disease, heavy bleeding and ovarian cancer. The new study sheds light on the potential and unique role that this procedure might play in heightening cardiovascular risk given that it abruptly stops the production of estrogen and other hormones and, depending on timing, can induce early onset menopause, which researchers said may be distinct from other causes of early menopause. We know that sex hormones, including estrogen and progesterone levels, play a crucial role in cardiovascular risk. Our study shows that there is an association between removing both ovaries and future development of heart failure, in particular. We believe this may be due to early menopause. However, in this case, early menopause results from the planned surgical removal of the ovaries, which differs from other causes such as occult infections, autoimmune diseases or unexpected genetic disorders. Understanding this allows us to anticipate and manage potential complications, particularly cardiovascular disease." Narathorn Kulthamrongsri, MD, first-year internal medicine resident, University of Hawaii, Honolulu The study uses data from 6,814 female patients who participated in the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2023. The average age of women undergoing the procedure was 43.6 years and 57 years for heart failure diagnosis. The ages at oophorectomy and heart failure onset were self-reported. Compared with women in the general population who have their ovaries, those who underwent a bilateral oophorectomy had a 1.5-fold increased risk of developing heart failure after adjusting for race, age, gender, diabetes, smoking status and high cholesterol. White women and those who had their ovaries removed at younger ages had an even higher, twofold increased risk of developing heart failure. "The age at which a woman has her ovaries removed appears to [impact] her heart failure risk," Kulthamrongsri said. "We found that as the age at which a woman has her ovaries removed goes up by one year, the development of heart failure happens about 0.6 years later." According to researchers, their findings also underscore the need to integrate cardiovascular risk discussions and closer heart monitoring for women contemplating oophorectomy before natural menopause (defined as not having a period for one full year), which usually occurs at 51 years of age, on average. "Women must do what is medically necessary in terms of oophorectomy, but our findings suggest they should have an informed discussion with their health care team about how to monitor their cardiovascular health and manage potential risk factors for heart failure, including adopting a healthy lifestyle as much as possible and perhaps asking about any potential role of hormone replacement therapy," Kulthamrongsri said. While some women may not have a choice in terms of when they undergo this procedure, for those who do, an informed discussion about the best timing based on their age and health is important to be able to discuss and weigh the potential added cardiovascular risks. This may be especially important for White women who appear to have a much higher risk of developing heart failure. "This racial disparity is surprising, as previous research shows that Black individuals have a higher prevalence of worse outcomes in heart failure due to greater risks of hypertension, diabetes and obesity. In contrast, White individuals more often develop heart failure from ischemic heart disease and tend to have more lifestyle-related risk factors, such as smoking, poor diet and physical inactivity. This finding might be explained by the etiology of heart failure that develops in early surgical menopause, related to myocardial infarction or other etiologies in which sex hormones play a crucial role," Kulthamrongsri said. The study is limited in that it relied on self-reported data and the researchers were only able to look at lifelong risk of heart failure rather than being able to determine if oophorectomy was more likely to lead to heart failure within a certain period after the procedure. However, Kulthamrongsri said the findings add to a growing body of evidence that early surgical menopause may have long-term cardiovascular consequences, particularly an increased risk of heart failure. This concern is especially relevant given the number of women who undergo oophorectomy procedures. Additional studies should be done to validate these findings using larger, global datasets. Future research should also explore possible preventive solutions, including cardiovascular screening recommendations and the use of prophylactic heart medications.

Women with polycystic ovary syndrome (PCOS) find it harder to get pregnant, have more frequent miscarriages and have a higher risk of developing endometrial cancer. Now, in a new study published in Nature Medicine, Swedish researchers have shown that the uterine lining of these women differs in terms of both the composition of individual cells and gene expression. The results open the door to new drug treatments. PCOS is the most common hormonal disorder affecting 11-13% of women of reproductive age. Women with the syndrome have difficulty getting pregnant and are at increased risk of miscarriage and uterine cancer, especially cancer of the endometrium. It is also common for affected women to be overweight and insulin resistant. By studying endometrial tissue samples from five healthy women and 12 women with PCOS, the researchers created a cell map of individual cells. The women were all of similar age, weight and BMI and the tissue samples were taken at the same phase of the menstrual cycle to eliminate factors that could influence the analyses. In the study, all women were overweight, but only the women with PCOS were insulin resistant and had elevated levels of male sex hormones. In total, almost 250,000 cell nuclei from the women's uterine linings were analyzed. The researchers found a clear difference in the composition of cell types with a higher proportion of so-called epithelial cells and a lower proportion of stromal cells in the uteruses of women with PCOS. These results show that the growth of the cells is affected, which may explain why it can take longer for affected women to become pregnant and why they are more likely to miscarry, as well as contributing to the increased risk of endometrial cancer." Elisabet Stener-Victorin, Professor of Reproductive Physiology at Karolinska Institutet and research leader of the current study In the detailed cell map, the researchers can show that many genes in specific cell types have a disturbed expression in women with PCOS. A large proportion of the affected genes are linked to difficulties for the early embryo to attach to the uterus, miscarriage and endometrial cancer with functions affecting cell-to-cell attachment and communication. "Our analyses show that certain cell types in the endometrium have disrupted communication and interaction specific to PCOS," says Gustaw Eriksson, one of the study's first authors and a doctoral student in Elisabet Stener-Victorin's research group. The study also included a part where the women with PCOS underwent treatment with the diabetes drug metformin with or without lifestyle advice on diet and exercise. After 16 weeks of treatment, the researchers found that many gene expressions in specific cell types, especially in the epithelial and stromal cells, were normalised by metformin, but also by lifestyle changes, although not as pronounced. "We can show that metformin seems to have many more functions in women with PCOS than lowering blood sugar. In the study, all the women were overweight, but it is likely that metformin has similar effects in affected women who are not overweight but insulin resistant if they have problems getting pregnant or have repeated miscarriages," says Elisabet Stener-Victorin. Another important finding was the correlation between gene expression in specific cell types and important clinical features of PCOS, such as elevated levels of male sex hormone and insulin resistance, highlighting the complex relationship between hormonal and metabolic factors and endometrial dysfunction. "As we identified changes in gene expression in specific cell types, this study provides crucial guidance for developing more targeted treatments for PCOS-related endometrial dysfunction," says Elisabet Stener-Victorin. The study is a collaboration with Dr Congru Li as joint first author, and Associate Professor Qiaolin Deng and Associate Professor Sophie Petropoulos with joint senior and corresponding authorship. The research was funded by the Swedish Research Council, the Novo Nordisk Foundation, the Diabetes Foundation and the Knut and Alice Wallenberg Foundation, among others.

Healthcare professionals need better support to help recognize and treat symptoms of disordered eating in people living with type 1 Diabetes, according to new research from the University of Surrey. Disordered eating in people living with type 1 Diabetes is often referred as T1DE. Diabulimia is one example of T1DE, a dangerous eating disorder which involves deliberate misuse of insulin for weight loss, leading to severe health problems and even death. New research from Surrey, led by Dr Katie Fitzgerald and supervised by Dr Rose-Marie Satherley, highlights the challenges healthcare professionals face in recognizing and treating T1DE. The study, published in Diabetic Medicine, has found that healthcare professionals face difficulties identifying and addressing T1DE in practice. This is due to a lack of support, limited confidence, and the fears of their patients' reactions and of damaging their patient-healthcare provider relationships. This may lead to delays in diagnosis and potentially life-threatening complications for patients. The study found that some healthcare professionals often perceived T1DE as an "inevitable" consequence of living with type 1 diabetes, leading to a sense of helplessness. This perspective, combined with a lack of training and clear guidelines, can contribute to missed opportunities for early detection and support. Dr Rose-Marie Satherley, co-author of the study and lecturer in Clinical Psychology at the University of Surrey, said: "Our study highlights the need for better training and clear clinical guidelines to support healthcare professionals in addressing disordered eating in adults with type 1 diabetes. The phrase "a bit of a black hole" that was used by one participant, aptly captures the uncertainty and confusion surrounding T1DE. "There is a real fear and lack of confidence these professionals are experiencing, so we must address the intersection of physical and mental health in diabetes care. We must equip our teams with psychological-expertise, effective communication strategies, as well with the tools and support they need to have these critical conversations to help improve their patients' health."

Many breast cancer (BC) survivors experience accelerated aging, potentially due to the cancer itself or the effects of various treatments. A recent study in Aging explored the relationship between Phenotypic Age Acceleration (PAA) and BC characteristics and treatments. Study: Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors. Image Credit: Ground Picture/Shutterstock.com Introduction Breast cancer is the most common cancer among women worldwide. However, early diagnosis and treatment significantly improve survival rates, with five- and ten-year survival rates at 91% and 85%, respectively. As a result, millions of women are living as BC survivors, including four million in the United States alone. Despite their extended lifespan, BC survivors often face faster cognitive decline and physical frailty compared to women without cancer. The study utilized a relatively new measure of aging—Phenotypic Age Acceleration (PAA)—to evaluate biological aging in BC survivors. PAA is calculated by combining chronological age (CA) with C-reactive protein (CRP, an inflammatory marker) and eight routine blood biomarkers, providing a cost-effective and accessible way to assess aging and predict mortality risk. Study participants The study included 1,264 BC patients and 429 cancer-free controls. BC patients were, on average, five years older than controls and had double the mortality rate (8% vs. 4%) over a median follow-up period of nine years. At diagnosis, 68% of patients were in stage I or II, while 17% had stage III/IV disease. High-grade tumors were present in 35% of cases, with intermediate-grade tumors in 39%. Nearly half (45%) of patients had hormone receptor-positive but HER2-negative (HR+/HER2-) BC, while 13% had HER2-positive BC and 14% had triple-negative BC (TNBC). Treatment varied widely. Surgery was the most common intervention, performed in nearly 90% of cases. Chemotherapy was used in 60% of patients, while 51% received radiation therapy and 66% underwent hormone therapy. Targeted therapy was administered to 17% of patients, but only 3% received immunotherapy. Over the follow-up period, 2% developed a second BC, and 20% experienced metastasis or recurrence. Study findings BC patients exhibited higher PAA than controls. At diagnosis, their phenotypic age (PA) exceeded their chronological age (CA) by an average of four years. This gap narrowed to two years at one-year post-diagnosis and one year at ten years, with no significant differences at two or five years. The degree of PAA varied based on several factors. Patients diagnosed at age 65 or older were initially phenotypically younger than their CA, but over time, they aged faster, surpassing their CA by 1.5 years at two, five, and ten years. Those with stage III/IV BC exhibited a five-year PAA at diagnosis, which persisted for ten years. High-grade tumors were linked to sustained accelerated aging, peaking at a three-year difference at one year and remaining two years higher at year ten. Cancer subtypes also influence aging patterns. HER2+ patients aged faster than HR+/HER2- patients, with a PAA of two years at year one and 1.5 years at year five. TNBC patients experienced an accelerated aging rate of 3.5 years at year one and two years at year two. However, by year ten, this trend reversed, and their PA was two years lower than their CA. Treatment impact on aging Different treatment modalities had varying effects on aging. Surgery appeared to have a protective effect, with patients showing a phenotypic age seven years younger than their CA at year ten. Radiation therapy alone resulted in a two-year reduction. When both were used together, the impact was similar to that of surgery alone. Chemotherapy and targeted therapy did not significantly impact PAA when administered alone. However, combination regimens that included chemotherapy led to accelerated aging by four years at one-year post-diagnosis. Patients who received hormone therapy—whether alone or alongside chemotherapy and targeted therapy—aged nearly three years faster than their CA at both one and ten years. Among chemotherapy agents, alkylating agents and anthracyclines initially increased PAA by two years at year one. However, this effect reversed over time, leading to a two- to 2.5-year reduction in PA at years five and ten. In contrast, antimetabolites, selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs) initially reduced PA by a year at year two. However, antimetabolites ultimately accelerated aging by seven years at year ten, while AIs added two years to the CA at the same time point. These findings suggest that hormone therapy may contribute to faster aging overall. Mechanisms of accelerated aging Accelerated aging in BC survivors may result from multiple factors. Cytotoxic chemotherapy can induce cellular senescence, telomere shortening, chronic inflammation, mitochondrial dysfunction, genomic instability, and epigenetic alterations. The study indicates that these effects may persist even ten years after diagnosis. Hormone therapy may also play a role by disrupting normal hormonal adaptation, genomic stability, and mitochondrial function, leading to stem cell exhaustion and increased biological aging. Conclusions “This study provides evidence of accelerated aging among BC survivors and identifies high-risk populations based on tumor characteristics and treatments.” Notably, this is the first study to apply PAA based on biochemical markers rather than epigenetic parameters in BC survivors. However, the findings must be interpreted cautiously due to selection and survival biases. Patients with high-grade tumors or aggressive treatments may have higher PAA but also higher rates of recurrence or death, potentially skewing results. Additionally, tumor characteristics primarily influence aging at diagnosis rather than during follow-up. Further research is needed to explore how demographic and lifestyle factors interact with aging-related outcomes in BC survivors, particularly with modern treatment regimens. These insights could help improve long-term care and quality of life for survivors.

For the first time scientists have identified promising drug candidates that bind irreversibly with a notoriously "undruggable" cancer protein target, permanently blocking it. Transcription factors are proteins that act as 'master switches' of gene activity and play a key role in cancer development. Attempts over the years to design "small molecule" drugs that block them have been largely unsuccessful, so in recent years scientists have explored using peptides – small protein fragments – to block these "undruggable" targets. Now researchers from the University of Bath have for the first time detailed an approach to discover peptides that bind selectively and irreversibly within cells, permanently blocking a transcription factor that drives cancer known as cJun. The team, publishing in the journal Advanced Science, used a new drug discovery screening platform technology, called the Transcription Block Survival (TBS) assay, which tests a huge number of peptides to "switch off" transcription factors that drive cancer. Their previous work identified reversible inhibitors of cJun, but this latest work builds on that by discovering peptides that bind selectively and irreversibly within cells, permanently blocking cJun action. The transcription factor cJun has two identical halves, which bind on either side of the DNA strand to alter gene expression. It can become overactive in cancer, driving uncontrolled cell growth, so the researchers designed a peptide inhibitor that binds to one half of cJun, stopping it from forming pairs and attaching to the DNA. Once they had made a peptide that bound to the transcription factor, the researchers modified it to bind irreversibly. The inhibitor works a bit like a harpoon that fires across to the target and won't let go – it grips the cJun tightly and stops it from binding to the DNA. We'd previously identified reversible inhibitors but this is the first time we've managed to block a transcription factor irreversibly with a peptide inhibitor." Dr. Andy Brennan, first author of the study and Research Fellow, University of Bath's Department of Life Sciences For the Transcription Block Survival assay, researchers inserted binding sites for cJun, into an essential gene in cells grown in the lab. As cJun binds to the gene, it prevents it working and the cell dies. In contrast, if cJun is blocked by the peptide inhibitor, the gene activity is restored and the cell survives. Jody Mason, CSO of Revolver Therapeutics and Professor of Biochemistry in the University of Bath's Department of Life Sciences, said: "Many drug candidates that are effective in vitro turn out to be toxic or don't penetrate cancer cells at all. "However our platform screens for peptide activity directly in the cell, overcoming many common challenges faced by drugs based on small molecules or antibodies. "The screen checks the activity of the inhibitor in a real cell environment which includes proteases and other proteins that can sometimes interfere with peptide activity, whilst also checking toxicity. "We hope this technology can in the future uncover other promising drug candidates for previously 'undruggable' targets." Having proven cell permeability and activity in cancer cells, as well as target selectivity, the researchers now need to show the inhibitors work in preclinical cancer models. The research was partly funded by the Medical Research Council and Biotechnology and Biological Sciences Research Council.

Integration of the NVIDIA BioNeMo platform enhances AI capabilities across the drug discovery lifecycle. Image Credit: Gorodenkoff/Shutterstock.com Sapio Sciences, the science-aware™ lab informatics platform, today announced the integration of the NVIDIA BioNeMo platform into the Sapio Lab Informatics Platform. This integration brings AI-driven computational drug discovery directly into Sapio ELN (Electronic Lab Notebook), helping to streamline workflows and improve decision-making in drug discovery. With the BioNeMo platform, researchers can accelerate drug discovery by leveraging science-specific AI frameworks, pre-trained models, and generative AI tools to streamline the identification of potential drug candidates and improve target selection accuracy. NVIDIA BioNeMo provides scientists with a framework for training and deploying large biomolecular language models at supercomputing scale. The integration of BioNeMo into the Sapio Platform provides scientists with embedded in silico tools, enabling them to, for example, generate novel candidate molecules early in the research process and test their docking with a target protein. With AI-driven molecular simulations available within a single, unified workflow, researchers can streamline their processes, enhance innovation, and accelerate the transition from discovery to development. Within Sapio ELN, researchers can access BioNeMo NIM microservices to rapidly identify and optimize drug candidates using AI-driven molecular modeling, including AlphaFold2 NIM for predicting accurate 3D protein structures; MoIMIM NIM to enable the design and optimization of small molecules; and DiffDock NIM, an AI-powered docking model developed by MIT. These models provide scientists with easy access to AI-driven tools without extensive setup, ensuring faster, more efficient research workflows. AI innovation is advancing rapidly, but scientists are often forced to navigate fragmented tools with complex interfaces, slowing down research. Our integration of NVIDIA’s powerful AI-driven tools directly into the Sapio Platform enables researchers to apply AI seamlessly into their experiments. Through this work, we are removing inefficiencies and equipping scientists with the tools to rapidly generate, analyze, and visualize both chemical and biological results." Kevin Cramer, Founder, CEO & CTO, Sapio Sciences Kevin continued: “We are working with NVIDIA to equip scientists and researchers with the most advanced AI tools to drive innovation in life sciences. This collaboration is a major step toward making AI an integral part of the drug discovery process, helping researchers make faster, data-driven decisions and improve research outcomes.” Anthony Costa, Director, Digital Biology at NVIDIA, commented: “Integrating BioNeMo into Sapio’s AI-driven research platform gives scientists access to advanced generative AI models for drug discovery. With AlphaFold2, MoIMIM, and DiffDock NIMs, researchers can predict, optimize, and validate drug candidates with greater speed and accuracy. This work underscores AI’s growing role in transforming pharmaceutical research and accelerating the path to breakthrough treatments.” Integrating NVIDIA technologies into the Sapio Platform is one of the many ways Sapio Sciences is helping to improve and accelerate biopharma discovery, clinical diagnostics, and drug manufacturing.