Caloric Restriction

088 - Fasting, Happiness, and the Skin-Gut Axis - HealthHippieMD Week In Review

A.I. Designs New Tools for DNA Editing

The realm of CRISPR gene editing is experiencing a technological revolution with the introduction of generative A.I. Profluent, a startup based in Berkeley, California, has unveiled an A.I. system that crafts blueprints for novel gene editing tools. This innovation, which employs methods similar to those driving the popular A.I. chatbot ChatGPT, can enhance the precision and speed of combating illnesses and diseases. Profluent's A.I. analyzes vast amounts of biological data to create gene editors that could surpass those formed through natural evolution. Their recent creation, OpenCRISPR-1, has already been used to edit human DNA and is now freely available for further experimentation. This breakthrough could herald a new era of medical treatments, tailor-made at unprecedented speeds. Generative A.I. Arrives in the Gene Editing World of CRISPR - The New York Times (gift article).

Skin-Gut Axis

Researchers at the University of California San Diego have discovered that skin injuries can significantly affect gut health in mice. This study reveals a skin-gut axis, showing that damage to the skin disrupts the intestinal defenses and alters the gut microbiome. The findings challenge the traditional belief that gut microbes primarily influence skin health, instead highlighting a bidirectional relationship. The experiments demonstrated that skin wounds and artificial increases in skin-specific enzyme levels led to more severe colitis, a gut disorder, by altering the microbial balance. This research, published in Nature Communications, suggests a new perspective on the interplay between skin injuries and gut health, with implications for understanding human diseases. A Skin-Deep Wound Can Trigger Gut Bacteria Changes: ScienceAlert (thanks, Amy).

Fever Dreams

Fever dreams, typically vivid, intense, and disturbing, are often a part of the ill experience when body temperature rises due to sickness. These dreams are characterized by bizarre, repetitive, and negative imagery, influenced by altered brain neurochemistry and rapid eye movement (REM) sleep disturbances. Research indicates these dreams often feature surreal scenarios and threatening elements, such as oversized creatures or menacing figures. Experts suggest fever-induced alterations in body and brain function could trigger these dreams, which also hold psychological significance, potentially representing inner fears or conflicts. While generally harmless, persistent fever dreams should be discussed with a healthcare provider as they could signal underlying health issues. What Does It Mean to Have a Fever Dream?

Fasting Time

Could a Calorie-Restricted Diet or Fasting Help You Live Longer? - The New York Times delves into the scientific intrigue surrounding calorie restriction and intermittent fasting as potential longevity boosters, a concept borne from decades of animal research. Studies suggest that cutting calorie intake can significantly extend the lifespan of various species, from worms to monkeys, by inducing key biological changes and reducing susceptibility to age-related illnesses like cancer. However, the application of these findings to human longevity remains uncertain. Although some evidence hints that these dietary adjustments could benefit human metabolic health and potentially slow aging, definitive long-term human studies are lacking, and the mixed results, including some contrary findings in human obesity, prompt ongoing debate among scientists.

Fact or Fiction

Chatbot answers are all made up. This new tool could help you figure out which ones to trust. | MIT Technology Review discusses a new tool developed by A.I. startup Cleanlab, aimed at evaluating the reliability of responses from large language models (LLMs). This tool, emerging from a quantum computing lab at MIT, scores outputs from LLMs on a scale from 0 to 1 to determine their trustworthiness, addressing businesses' concerns about these models' tendency to "hallucinate" or generate inaccurate information. By providing a reliability score, the tool allows users to discern which responses to trust. This innovation is especially pertinent as chatbots become more integrated into daily digital interactions, from search engines to office software. The Trustworthy Language Model could significantly reduce the risk of using LLMs in high-stakes business environments, enhancing their appeal and utility.

Sweet Nothings

In a recent article from The Atlantic, the introduction of brazzein, a new sugar substitute, is explored alongside older alternatives like aspartame and stevia. Despite its promise, brazzein must replicate sugar's unique sweetness, much like its predecessors. The narrative recounts a personal journey of managing blood sugar levels through various sweeteners, underscoring the dissatisfaction with their aftertaste and health concerns. Even with technological advancements, sugar substitutes still mimic sugar's flavor and texture, leading to continued disappointment for those seeking a healthier, yet equally satisfying, alternative to sugar. A New Sweetener Has Joined the Ranks of Aspartame and Stevia - The Atlantic

Happiness: Marriage and Money

The Happiness Trinity - The Atlantic delves into the complex question of what truly fuels our happiness. Marriage, according to W. Bradford Wilcox's new book, Get Married: Why Americans Must Defy the Elites, Forge Strong Families, and Save Civilization, emerges as a significant predictor of life satisfaction in America, outshining education, income, and job satisfaction. However, the discourse extends beyond matrimony, exploring "social fitness" — the quality of relationships in one's life — as an even stronger happiness determinant. The article also highlights the intertwined roles of income and social well-being, noting that higher income levels correspond with better marriage and social outcomes. Ultimately, the discussion suggests that happiness in America might morph into a luxury, stratified by income levels, with significant implications for society's overall well-being.

Unraveling the Complexities of Consciousness

The quest to understand consciousness remains elusive, yet tantalizing advances have sparked renewed interest. Grounded in the Orchestrated Objective Reduction (Orch OR) theory, pioneered by Roger Penrose and Stuart Hameroff, researchers posit that consciousness emerges from quantum processes within brain microtubules. Recent explorations extend this theory, demonstrating that microtubules might maintain quantum coherence far longer than expected, suggesting that our brains can sustain these quantum states despite their warm, wet conditions. Complementarily, Timothy Palmer's Invariant Set Theory proposes that consciousness and free will reflect our entanglement in a universal fractal geometry. While far from conclusive, these insights offer intriguing possibilities about the structure and reach of consciousness, bridging scientific inquiry with profound philosophical implications. Where Does Our Consciousness Live? It's Complicated.

011 - CVS, Amazon, and the Disruption of Primary Care, Anxiety Inoculants, Wabi Sabi, and AI. - HealthHippieMD Week In Review

Wabi Sabi - An Inoculant for Perfectionism

Perfectionism can have a devastating effect on mental health. The Japanese concept of wabi-sabi can help: Escape the perfectionist trap with the philosophy of "wabi-sabi"

CVS, Amazon, and the Disruption of Traditional Primary Care

Traditional primary care practices and healthcare systems should be quaking in their boots. The article CVS, Amazon Deals Might Be Good for Patients, Bad for Primary Care, gives the good and bad of the disruption of healthcare. We are in the early days of this transformation that will include technology and place a much greater emphasis on preventative care/wellness. Exciting times!

+For some of the challenges, see this article extracted from a recent Harvard Business Review: Amazon's Foray into Primary Care Won't Be Easy "....a fundamental question looms: Can profit-driven entrepreneurship and bottom-up innovation make the U.S. health care system work anywhere nearly as well as those in places like France, Sweden, Norway, Australia, the Netherlands, New Zealand, Germany, and Switzerland? They may be relatively dull, but they keep people healthy at an affordable cost.".

How to be Bold

Anxiety short-circuits many decision-making processes for a wide range of the population. The article How to Be Bold discusses the implications and how to overcome anxiety inertia. Thanks, Laura!

Fasting and Cancer

I am interested in extending lifespan and health span, so I have read many papers on caloric restriction. Fasting to combat cancer is somewhat controversial but gaining momentum. Dr. Michael Gregor over at NutritionFacts has a great series of introductory videos for you:

+For a decent scientific review on caloric restriction and cancer, see this 2018 paper from Valter Longo's Lab: Starvation, Stress Resistance, and Cancer

Immersive Rights in the Metaverse

The Metaverse, "a broad societal shift in how we engage digital content, going from flat media viewed in the 3rd person to immersive experiences engaged in the 1st person," is coming, ready or not. As with all powerful technologies, we must consider their use and implications. The article The case for demanding "immersive rights" in the Metaverse touches on many of the potential issues. This article reminded me of some of the early warnings on the use and potential abuse of social media.

Immersive Virtual Environments Eases Pain During Hand Surgery

The article, Gaming tech could ease pain during surgery, reports the findings of a recent preliminary study looking at the effects of immersive VR on surgical pain: Virtual reality immersion compared to monitored anesthesia care for hand surgery. Adding this to my reading list.

Life Lessons Gleaned from Free Soloing El Capitan

The advice and life lessons came rapidly in the podcast, How free solo climber Alex Honnold faces fear. The interviewer, Adam Grant, an organizational psychologist at Penn, was positively giddy during the interview. This episode is well worth your time.

Rethinking Alzheimers

Last week I mentioned the re-examination of a foundational paper whose findings have been questioned. That re-examination, coupled with the little to no progress in the prevention or treatment of the disease, has led to renewed interest in alternate theories. The article Alzheimer's Might Not Be Primarily a Brain Disease, examines some of the leading alternate views.

A panel of experts gathered by the U.S. Department of Health and Human Services issued a draft guidance this week recommending all adults 65 and younger are screened for anxiety: Health Panel Recommends Anxiety Screening for All Adults Under 65. One of the issues mentioned is what the U.S. will do with the increased volume of newly diagnosed anxious adults. The mental health infrastructure was inadequate before the pandemic. During the pandemic, the existing volume of patients struggled to find licensed mental health providers. It is unlikely the system will be able to keep up with all the newly diagnosed patients in need of services.

Stool Banking - Your Poop May Hold the Secret to Longevity

As we learn more about the microbiome and the aging process, the two are intertwined--especially around inflammation. Ten years ago, when trying to convince my chairman about the importance of this emerging area, I remember telling him that as we learn how important the microbiome is to health and wellbeing, the inevitable outcome would be the prevalence of personal stool banking. The article Your Poop May Hold the Secret to Long Life focuses on the logistical and ethical questions surrounding storing your stool.

Eric Topol

Eric Topol is constantly tweeting out fantastic resources. My favorite finds from this week:

Humans Evolved with their Microbiomes

The gut microbiome plays many vital roles in health and well-being. Humans evolved with their microbiomes, and like genes, gut microbes pass from one generation to the next discusses the co-evolution of humans and their microbial passengers.

The Search for New Pain Medication

The Economist had a great article on the search for new analgesics: Better medicines are needed to relieve pain

Quote of the Week

"Blind belief in authority is the greatest enemy of truth." - Albert Einstein.

010 - Caloric Restriction, Vulnerability Hangovers, and Psychobiotics - HealthHippie Week In Review

Caloric Restriction and Healthspan

An email from the NIH, Calorie restriction, immune function, and health span gave an overview of a recent publication in Science focused on the immune system. In humans, the primary study (called the CALERIE Study) found caloric restriction led to changes in gene activity in body fat and related immune cells. Those that underwent caloric restriction had more prominent, less fatty thymi than controls. Based on findings in the original study, these authors studied a gene (Pla2g7) in mice. Mice who lacked this gene had less inflammation, larger thymi, gained less weight from eating a high-fat diet, burned more fat, and were less likely to develop fatty liver disease than the controls. The authors are trying to identify potential therapeutic targets to enhance longevity.

+If you're interested in this topic, Peter Attia's recent conversation with Matt Kaeberlein, How nutrition impacts longevity, is an insightful discussion. Although sadly, there is not a single mention of the microbiome.

Melanoma and the Microbiome

Within the last several years, there has been convincing evidence that dietary choices (specifically increasing dietary fiber) positively influence the efficacy of melanoma immunotherapy by way of the microbiome: Fiber boosts melanoma patients' response to immunotherapy In a recent paper, unsurprisingly, broad-spectrum antibiotics, at least in mice, seem to have the opposite effect, accelerating tumor growth: Melanoma: Gut microbiome-depleting antibiotics may make it worse

ARPA-H

President Biden named the head of the new Biomedical Research Agency, focused on fighting cancer and other diseases. The new agency, ARPA-H (Advanced Research Projects Agency-Health), jumpstarted by a $1 billion investment from Congress, is modeled after the military's futuristic Defense Advanced Research Projects Agency (DARPA). ARPA-H focuses on high-risk, high-reward areas of innovation. Biden Picks Biotech Executive to Lead New Biomedical Research Agency. Exciting times!

An Overview of Brain Fog

The NY Times had a fascinating overview of brain fog: What Is Brain Fog and How Can I Treat It?

+More on brain fog by one of my favorite science writers: Ed Yong on One of Long COVID's Most Misunderstood Symptoms

CRISPR Musings

Jennifer Doudna was co-recipient of the Nobel Prize in Chemistry for her discovery of CRISPR: Nobel Prize Awarded to Jennifer Doudna And Emmanuelle Charpentier For CRISPR Discovery This week, Dr. Doudna published her thoughts on CRISPR in the Atlantic: Starting a CRISPR Revolution Isn't Enough I highly recommend Walter Isaacson's fantastic biography, The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race.

Does Psychological Stress Increase the Incidence of Long Covid?

This study offers some preliminary evidence that it does: Psychological distress may increase your odds of getting long Covid, study finds.

Why Do Some People Seem Immune to Covid?

Scientists are trying to figure out why: The Mystery of Why Some People Don't Get Covid. Interestingly, there is no mention of interest in the microbiome, which we know influences immunity.

Exercise and Immunity

As if you needed another reason to exercise: The article, Can Exercise Strengthen Your Immunity, gives a synopsis of a recent meta-analysis published in the British Journal of Sports Medicine. The authors of the study found preliminary evidence they believe showed both a protective effect for contracting Covid and a lower likelihood of experiencing severe Covid. Interpretation of the results is controversial, but few argue the overall positive impact of exercise on health.

Alzheimer's Uproar

You've likely seen news stories about a foundational Alzheimer's paper whose findings were recently called into question. The podcast episode, An Alzheimer's uproar, explains the controversy.

+Tools to tease out scientific misconduct: Fake research can be harmful to your health – a new study offers a tool for rooting it out.

Talking to Strangers

When meeting a new person, the prevailing wisdom is you should listen more than you speak. A recent study shows that strategy is wrong: People think they should talk less to be liked, but new research suggests you should speak up in conversations with strangers.

+The benefits of talking to strangers: Why talking to strangers is good for you, them, and all of us.

Vulnerability Hangovers

Shared a little too much with a friend last night? The New York Times has you covered: How to Nurse a Vulnerability Hangover

The Wandering Mind

"...mind-wandering is rarely a waste of time. It is merely our brain trying to get a bit of work done when it is under the impression that there isn't much else going on." Unhappy minds wander in the past, while happy minds often ponder the future." Scientists finally know why we get distracted — and how we can stay on track

CAR-T for Auto-Immunity

CAR-T drugs, today, are used primarily in hard-to-treat cancers. A recent manuscript, Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus, shows how these "living drugs" may play a role in the treatment of autoimmune diseases: How a 'Living Drug' Could Treat Autoimmune Disease

Mental Health, Food, and the Microbiome

Nutritional psychiatry and psychobiotics are reaching popular consciousness. As I was readying this newsletter for publication, the article, Nutritional approaches targeting gut microbiome could improve brain disorders, hit my inbox. Adding the paper, Diet and the microbiota–gut–brain-axis: a primer for clinical nutrition to my reading list.

Quote of the Week

“History doesn't repeat itself, but it often rhymes” – Mark Twain