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Brian Kennedy is a renowned biologist, leader in aging research, and director of the Center for Healthy Longevity at the National University of Singapore. In this episode, Brian shares insights from ongoing human aging studies, including clinical trials of rapamycin and how dosing strategies, timing, and exercise may influence outcomes. He presents two key models of aging—one as a linear accumulation of biological decline and the other as an exponential rise in mortality risk—and explains why traditional models of aging fall short. He also explains why most current aging biomarkers lack clinical utility and describes how his team is working to develop a more actionable biological clock. Additional topics include the potential of compounds like alpha-ketoglutarate, urolithin A, and NAD boosters, along with how lifestyle interventions—such as VO2 max training, strength building, and the use of GLP-1 and SGLT2 drugs—may contribute to longer, healthier lives.

We discuss:

• Brian’s journey from the Buck Institute to Singapore, and the global evolution of aging research [2:45];
• Rethinking the biology of aging: why models like the hallmarks of aging fall short [9:45];
• How inflammation and mTOR signaling may play a central, causal role in aging [14:15];
• The biological role of mTOR in aging, and the potential of rapamycin to slow aging and enhance immune resilience [17:30];
• Aging as a linear decline in resilience overlaid with non-linear health fluctuations [22:30];
• Speculating on the future of longevity: slowing biological aging through noise reduction and reprogramming [33:30];
• Evaluating the role of the epigenome in aging, and the limits of methylation clocks [39:00];
• Balancing the quest for immortality with the urgent need to improve late-life healthspan [43:00];
• Comparing the big 4 chronic diseases: which are the most inevitable and modifiable? [47:15];
• Exploring potential benefits of rapamycin: how Brian is testing this and other interventions in humans [51:45];
• Testing alpha-ketoglutarate (AKG) for healthspan benefits in aging [1:01:45];
• Exploring urolithin A’s potential to enhance mitochondrial health, reduce frailty, and slow aging [1:05:30];
• The potential of sublingual NAD for longevity, and the combination of NAD and AKG for metabolic and exercise enhancement [1:09:00];
• Other interventions that may promote longevity: spermidine, 17𝛼-estradiol, HRT, and more [1:17:00];
• Biological aging clocks, clinical biomarkers, and a new path to proactive longevity care [1:23:15];
• Evaluating rapamycin, metformin, and GLP-1s for longevity in healthy individuals [1:32:15];
• Why muscle, strength, and fitness are the strongest predictors of healthspan [1:37:30];
• Why combining too many longevity interventions may backfire [1:39:30];
• How increased funding and AI integration could accelerate breakthroughs in aging research [1:41:45];
• The research Brian is most excited about, and the need to balance innovation with safety in longevity clinics [1:47:00];
• Peter’s reflections on emerging interventions and the promise of combining proven aging compounds [1:54:00]; and
• More.

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In this episode from July 2022, Peter dives deep into the topic of bone health and explains why this is an important topic for everyone, from children to the elderly. He begins with an overview of bone mineral density, how it’s measured, how it changes over the course of life, and the variability between sexes largely due to changes in estrogen levels. From there he provides insights into ways that one can improve bone health, from exercise to nutrition supplements to drugs. Additionally, Peter discusses what happens when one may be forced to be sedentary (e.g., bedrest) and how you can work to minimize the damage during these periods.

While this original episode is an AMA, it is available in full to all listeners as a special rebroadcast.

We discuss:

• Overview of bone health topics to be discussed [2:30];
• Bones 101: bone function, structure, and more [6:15];
• Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [9:30];
• The consequences of poor bone health [14:30];
• The devastating nature of hip fractures: morbidity and mortality data [18:00];
• Where fractures tend to occur in the body [23:45];
• Defining osteopenia and osteoporosis [25:30];
• Measuring BMD with DEXA and how to interpret scores [28:00];
• Variability in BMD between sexes [35:15];
• When should people have their first bone mineral density scan? [37:45];
• How BMD changes throughout the life and how it differs between men and women [40:15];
• How changes in estrogen levels (e.g., menopause) impact bone health [45:15];
• Why HRT is not considered a standard of care for postmenopausal bone loss [49:00];
• Factors determining who may be at higher risk of poor bone health [52:00];
• Common drugs that can negatively impact BMD [55:45];
• How children can optimize bone health and lay the foundation for the future [59:30];
• Types of physical activity that can positively impact bone health [1:03:30];
• How weight loss can negatively impact bone health and how exercise can counteract those effects [1:12:15];
• Nutrition and supplements for bone health [1:16:00];
• Pharmaceutical drugs prescribed for those with low BMD [1:18:45];
• Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:23:30]; and
• More.

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Tanuj Nakra and Suzan Obagi, two leading experts in aesthetic medicine, join Peter to explore the science of facial aging and skin health as well as the responsibilities physicians face in the world of cosmetic procedures. In this episode, they examine the biological and hormonal drivers of facial aging, the evolutionary and psychological foundations of attractiveness, and the impact of modern media on beauty standards. They discuss the rise in cosmetic procedures among adolescents and the ethical responsibilities of physicians in these cases. The conversation then shifts to a practical, evidence-based guide to skin health—covering the use of mineral sunscreens, retinoids, vitamin C, and tailored skincare routines, as well as the management of acne and the psychology behind aesthetic consultations. The episode culminates in a candid, personal assessment of Peter’s own face, offering a revealing look at what aesthetic medicine can achieve and how to think critically about pursuing it.

We discuss:

• Tanuj’s and Suzan’s training and expertise, and the evolving field of aesthetic medicine [4:00];
• The biology of the aging face [10:45];
• Why facial fat atrophies with age while body fat tends to accumulate [17:00];
• How chronic stress accelerates facial aging [20:30];
• The evolutionary biology of beauty, and how modern lifestyle, culture, and medicine interact with these ancient aesthetic instincts [25:30];
• How social media and influencers have rapidly shifted aesthetic trends toward exaggerated features and unrealistic beauty standards [36:45];
• The ethical challenges, financial incentives, and social pressures shaping modern aesthetic medicine [42:00];
• The concerning trend of teenagers seeking cosmetic enhancements: the ethical and cultural impact of early beauty pressure [51:45];
• Protecting the skin: UV damage and sunscreen recommendations [58:15];
• Strategies for minimizing skin aging: retinoids, vitamin C, and evidence-based application methods [1:09:00];
• Effective daily skincare routine: cleansing, antioxidants, retinoids, moisturization, and more [1:18:45];
• The playbook for managing acne [1:31:00];
• The 4 changes of aging and the complexities of aesthetic consultations including the anatomical, psychological, and ethical factors physicians must navigate [1:39:00];
• The 5 R’s of rejuvenation [1:50:15];
• A facial aging analysis and cosmetic strategy using Peter’s face as a real-time case study [1:53:00];
• The decision-making process between fat grafting and dermal fillers for facial rejuvenation [1:56:30];
• How self-image, eye aesthetics, and fleeting photos drive the desire for cosmetic enhancement [2:01:45];
• Advice for wrinkles, causes of dark circles under the eyes, and the importance of facial symmetry [2:05:45];
• Considerations that shape clinical decision making around fat grafting and other procedures to address the eye area [2:11:00];
• The evolution of facial cosmetic surgery techniques, the serious risks involved, and how physician skill and procedure selection greatly impact outcomes [2:21:30];
• How patients can make informed and safe choices when selecting a cosmetic surgeon [2:27:15];
• A comparison of ablative versus non-ablative skin resurfacing treatments, laser vs. peels, and more [2:38:45];
• How treatments are chosen and customized based on patient-specific factors [2:48:00];
• The lifelong human desire to align physical appearance with self-identity [2:52:45]; and
• More.

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BJ Miller, a hospice and palliative care physician, and Bridget Sumser, a licensed social worker specializing in serious illness and end-of-life care, join Peter to share insights from their decades of work supporting people at the end of life. In this episode, they explore the emotional and physiological processes of dying, the cultural barriers that prevent meaningful conversations about death, and how early engagement with mortality can lead to greater clarity and connection. The conversation highlights the distinctions between hospice and palliative care, the nature of suffering beyond physical pain, and the transformative role of honesty, forgiveness, and relational awareness in the dying process. Through stories and reflections, BJ and Bridget reveal what truly matters in the end—and how the dying can teach the living not only how to face death but how to live more fully.

We discuss:

• The personal journeys of BJ and Bridget into end-of-life care, and the connection between living and dying [3:30];
• What dying looks like: the physical, cognitive, and emotional realities at the end of life [13:15];
• How historical perspectives on death contrast with modern experiences of dying [25:30];
• The difference between palliative care and hospice care [30:45];
• The systemic challenges surrounding hospice care: why patients often enter it too late to receive its full benefits [35:30];
• How delayed hospice referrals and unspoken preferences often prevent patients from dying where and how they truly want [39:30];
• The realities of home hospice: challenges, costs, and burdens placed of families [43:45];
• How proactively engaging with the reality of death can avoid unnecessary suffering and promote a more peaceful ending [53:30];
• How palliative care is misunderstood and underutilized—especially in cancer care [1:02:45];
• Palliative care in the case of Alzheimer’s disease: emotional support, future planning, and family involvement [1:12:15];
• The importance of having an advance directive: defining what matters most before it’s too late [1:23:00];
• The differences between how young and old individuals experience dying from cancer [1:30:15];
• The difference between pain and suffering, role of medicine in pain relief, and why emotional healing is essential at the end of life [1:35:45];
• Dying well: the power of self-honesty and human connection at the end of life [1:47:00];
• How psychedelics like psilocybin can unlock emotional breakthroughs and deepen connection for patients near the end of life [1:55:15];
• Lessons from the dying on how to live well [1:57:30];
• The physical process of active dying, and the emotional and practical considerations for loved ones [2:09:30]; and
• More.

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This is part two of a two-part mini-series on fertility and reproductive health. Paula Amato is a leading expert in female reproductive health and infertility, widely recognized for her contributions to advancing fertility treatment and research. In this episode, which follows last week's conversation on male fertility, Paula explores the biology of female fertility, including how hormonal changes regulate the menstrual cycle and ovulation, what those patterns reveal about fertility potential, and why both partners should be evaluated early in infertility workups. She discusses the role of the fallopian tubes, the causes of miscarriage, the impact of age and lifestyle on fertility, and treatment options for conditions like PCOS—including the emerging use of GLP-1 agonists. The episode also covers the evolution of IVF, advances in pre-implantation genetic testing, egg freezing, and the promise and limitations of next-generation reproductive technologies.

We discuss:

• The finite nature of a woman’s egg reserve, how it changes over time, and the basic process of ovulation and fertilization [3:00];
• How hormones influence egg selection, and how and why chromosomal errors lead to most miscarriages [5:30];
• The full journey of conception—from hormonal cues triggering ovulation, to fertilization, embryo development, implantation, and early pregnancy risks [16:30];
• How infertility is defined and diagnosed, and the broader trends contributing to rising infertility rates [25:15];
• Fallopian tube damage: how STDs and scarring impact fertility and raise ectopic pregnancy risk [31:30];
• Unexplained infertility: how doctors evaluate ovulation and cycles—and why more research on women’s health is needed [41:00];
• The defining symptoms of polycystic ovary syndrome (PCOS), its hormonal characteristics, and its relationship with insulin resistance [44:00];
• Managing PCOS without pregnancy: cycle regulation, androgen suppression, and insulin resistance treatment [46:00];
• The treatment approach for women with PCOS who are trying to conceive: GLP-1 use, ovulation induction, and timing protocols [49:45];
• Barriers to getting informed fertility care for PCOS: limited provider knowledge and access, insurance gaps, and next steps when ovulation treatments don’t lead to pregnancy [55:45];
• Fertility treatment for women with unexplained infertility, risk of multiple pregnancies with superovulation, and more [1:03:00];
• Intrauterine insemination (IUI): process, success rates, and when in vitro fertilization (IVF) becomes the better option [1:07:00];
• The history of in vitro fertilization (IVF), and how access and acceptance have evolved over time [1:16:45];
• The step-by-step process of IVF [1:19:30];
• The IVF lab process: egg retrieval, fertilization, embryo culture, and freezing [1:26:30];
• Genetic testing and embryo selection in IVF: aneuploidy screening, polygenic traits, and ethical concerns [1:41:15];
• Embryo transfer in IVF: timing, uterine preparation, and implantation support [1:47:30];
• Egg donation in IVF: indications, donor guidelines, and other considerations [1:50:45];
• How to choose the right IVF clinic [1:54:45];
• Innovations in fertility on the horizon, advice about freezing eggs, and more [2:02:00];
• Optimizing fertility through lifestyle: diet, stress management, sleep, exercise, and supplementation [2:07:45];
• Promising areas of fertility research [2:15:45]; and
• More.

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This is part one of a two-part mini-series on fertility and reproductive health, with next week's guest, Dr. Paula Amato, focusing on the female side of the equation. Paul Turek is a world-renowned expert in male fertility and reproductive health, the founder and medical director of the Turek Clinic, and host of the Talk with Turek podcast. In this episode, Paul explores the topic of male fertility, offering a detailed look at the complex and highly coordinated process of conception and the many challenges sperm face on their journey to fertilizing an egg. He shares fascinating insights into how sperm work together to navigate the female reproductive tract, how environmental factors like heat, stress, and toxins impact sperm quality, and what men can do to improve their reproductive health. Paul also dispels common myths about testosterone replacement therapy and its effects on fertility, providing strategies for preserving fertility while on TRT. The episode also highlights cutting-edge advances in reproductive medicine, from genetic testing and sperm sorting to emerging treatments for infertility.

We discuss:

• The incredibly complex and hostile journey sperm must take to fertilize an egg [3:00];
• How sperm are made: meiosis, genetic variation, and the continuous renewal influenced by environmental factors [9:00];
• The built-in filter that weeds out genetically abnormal sperm [14:45];
• How sperm are finalized in form and function: tail formation, energy storage, and chemical sensing abilities [18:30];
• How to optimize conception through the timing of sex, ejaculation frequency, and understanding the sperm lifecycle [26:30];
• Male infertility and Paul’s diagnostic approach: detailed history, a physical exam, and identifying red flags [33:30];
• Viral infections that can affect the testes and potentially lead to sterility [40:30];
• Semen analysis: morphology, motility, and hormonal clues to male fertility [45:45];
• Effects of medication, microplastics, stress, and exercise on fertility [57:15];
• Testosterone replacement therapy (TRT) and male fertility [1:06:00];
• Restoring fertility after prolonged use of exogenous testosterone [1:25:00];
• Effects of heat and cold exposure on fertility and sperm quality [1:36:00];
• How different levels of exercise—especially cycling—affect male fertility [1:41:45];
• How alcohol, marijuana, and nicotine affect male fertility [1:46:00];
• Why type 2 diabetes is a risk factor for male infertility [1:50:00];
• How varicoceles—a common cause of male infertility—are diagnosed and treated [1:51:15];
• Genetic factors that affect fertility [1:54:00];
• The impact of lifestyle and environmental exposures on fertility [1:56:30];
• The evidence (or lack thereof) behind stem cell and PRP therapies for male infertility, and how lifestyle and non-invasive interventions often lead to successful conception [2:00:30];
• Considerations for sperm banking, and how paternal age impacts fertility planning and offspring health [2:05:00];
• Semen quality as a biomarker: linking male fertility, longevity, and preventative health through Medicine 3.0 and epigenetics [2:14:45]; and
• More.

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