"To lengthen thy life, lessen thy meals." ~Benjamin Franklin

A major public health concern of our 21st century society is overeating and inactivity which has led to ~42.4% of the US population being classified as obese(1) defined as having a body mass index of greater than 30. Obesity is a risk factor for many severe diseases including cardiovascular disease, type 2 diabetes, stroke, and kidney problems. Despite awareness of these risks the incidence of obesity is increasing with no clear resolution in sight. There is a long history of experiments demonstrating that reducing the amount of food eaten increases healthy lifespan. First shown in a 1935 study by C. M. McCay that rats receiving less food attained extreme ages with less frequency of disease(2). It should be noted that to achieve these beneficial results to health and longevity the diet must be well balanced and lack any nutritional deficiencies. Simply starving yourself won’t cut it, obviously. This has been replicated in other animals including primates (rhesus monkey) and is a continued area of study nearly a century later(3).

During the early history of humanity, we did not have the regular three meals per diem and would often go several days without eating. Our bodies evolved under these conditions and are prepared for periods of intermittent fasting. It may even benefit our health in many ways. In this post I will review the science of caloric restriction, its cellular and molecular mechanisms, its role in maintaining proper circadian rhythm, a strong immune system and proper glucose-insulin signaling. An organism’s ability to maintain a relatively stable equilibrium of internal, physical and chemical conditions ideal to its survival is known as homeostasis. The systems that maintain homeostasis are linked to ancient survival circuits ubiquitous amongst living organisms. You may think that optimum health is achieved by keeping strict homeostasis of all our vital living conditions but as it turns out, getting a little bit outside your comfort zone may build resilience and strength. This concept is known as hormesis which suggests that there may be bioprotective advantages to low level exposure to several environmental stimuli including temperature, DNA repair, antioxidant function, apoptosis and immune response.

"He who buries his head deep into a nosebag full of food cannot hope to see the invisible world." ~Al-Ghazali

Most of us grew up with the phrase “breakfast is the most important meal of the day,” but as it turns out this may have been more to do with marketing than public health. Even talking to most nutritionists today they will emphasize breakfast and eating consistent snacks throughout the day. As new research comes out on the effects of caloric restriction and intermittent fasting in healthy humans it may be time to rethink many of our eating habits and culture around food.

Health benefits of caloric restriction

One of the few experimentally validated ways to extend lifespan in mammals is to reduce the total amount of food consumed, also known as caloric restriction. While the average lifespan has been steadily increasing primarily due to decreased infant mortality rate and increased recovery and resistance to infectious disease, the maximum lifespan hasn’t improved much for humans(4). There is an inverse relationship between the total caloric intake in mammals and their average as well as maximum lifespan(5). This extension of life was observed even when caloric restriction was initiated in middle aged mice, although the greatest extension was seen in mice with a restricted diet their entire lives. While these changes may takes years of commitment to observe changes in lifespan other beneficial effects such as reduced blood glucose and insulin levels have been reported after only a few days to a few months but return to normal after the modified diet has been ended(6). There is evidence that caloric restriction achieves an anti-inflammatory response by increasing cellular oxidative stress, decreasing reactive oxygen species (ROS), increasing bioavailability of NO leading to a suppression of vascular disease progression and aging effects(7).

"Fasting today makes the food good tomorrow." ~German Proverb

Sirtuins are a set of evolutionarily conserved genes that regulated metabolic activity and DNA repair that aid in signaling the body (or cell) to slow down reproduction and focus on rejuvenation. Dr. David Sinclair, a professor researching aging at Harvard, has hypothesized that this ancient survival circuit was one of the first genes evolved by our primordial single cell ancestors that enabled them to ‘hunker down’ in times of stress allowing for enhanced DNA repair at the cost of cellular division or reproduction. Bypassing the primal evolutionary urge to reproduce at all costs, this sensor circuit is still linked to metabolic fitness and longevity today and is the foundations of the company Elysium (https://www.elysiumhealth.com/en-us/science-101/why-sirtuins-are-important-for-aging). SIRT1, one of the seven sirtuins in humans, is induced by caloric restriction, and by fasting(7). Boosting expression of sirtuins has been shown to extend lifespan in worms(8), flies(9), fish(10), and mice(11). Sirtuins are Nicotinamide adenine dinucleotide (NAD) dependent enzymes which is a major hub in metabolism that you may remember from high school biology for its role in glycolysis and oxidative phosphorylation. SIRT3 is found in high levels in brown adipose tissue and increases expression in response to exercise and cold exposure(12).

When I was young, I observed a couple from Germany sitting in the snow, calm and collected and asked my dad, why are they doing that? We tried it out ourselves and enjoyed the cold shock and adaptation that occurred by trying to tough it out and the tingles that occurred when we jumped back into the lukewarm swimming pool in the Colorado mountains. I just did it to be adventurous and try new things, but I may have been setting up my brown fat and sirtuins for success! Dr. David Sinclair suggests this in his book Lifespan: Why We Age—and Why We Don’t Have To (https://www.amazon.com/gp/product/1501191977/ref=as_li_tl?ie=UTF8&camp=1789&creative=9325&creativeASIN=1501191977&linkCode=as2&tag=yogasciencear-20&linkId=9a4df30ff2122b52b192929c76fc7b72) that all the hallmarks of aging may have a single cause related to mis-regulated sirtuins and NAD availability:

1. Genomic instability and DNA damage
2. Degradation of telomeres
3. Epigenetic dysregulation
4. Disruption of proteostasis, normal protein regulation
5. Deregulation of nutrient sensing and metabolism
6. Mitochondrial dysfunction
7. Cellular senescence
8. Stem cell depletion
9. Buildup of extracellular debris
10. Disrupted intracellular communication
11. Increased production of inflammatory molecules

Caloric restriction has been studied in primates since the early 1990’s and found to be safe (13), and have beneficial effects in terms of body weight, and body fat compared to control rhesus monkeys (14). A longer term study of rhesus monkeys started caloric restriction later in life (18.5 to 21.5 years old) and found that after 9 years the animals on the caloric restriction diet had improved survival, body weight, fasting glucose levels, and age-related morbidity (15). While there have been some contradictory results indicating no beneficial effect, this is likely due to methodological explanations such as not providing enough water for the animals on caloric restriction(16).

Intermittent Fasting

“There is evidence to suggest that the circadian rhythm fasting approach, where meals are restricted to an eight to 10-hour period of the daytime, is effective” – Dr. Deborah J. Wexler

An alternative to simply reducing the amount of food eaten is to restrict the period of eating also known as intermittent fasting. Humans, and most animals, evolved under conditions of intermittent fasting leading our biochemistry and genetics to be tuned to handle days without eating. In our modern culture endorsing three square meals a day in addition to treats, brunch, and midnight snacks, the idea of fasting may sound like blasphemy but in many ways is returning to our ancestral diet. Here are the most common eating schedules to implement intermittent fasting:

1. Time Restricted Eating also known as 16:8
2. Eat-Stop-Eat also known as 5:2
3. Alternate day fasting
4. OMAD – One Meal A Day

Time restricted eating is a type of intermittent fasting that involves limiting the time of day that eating occurs, typically a 16 hour fast each day with an 8-hour eating window. This can be achieved by skipping breakfast and late-night snacks. This is one of the few methods that has shown promising results when tested in humans(17). Although this study investigated people with metabolic syndrome (a precursor to diabetes) the results showed improvements in weight loss, reduced waist size, lower blood pressure, and reduced lipids and cholesterol levels. It is as yet unverified to have beneficial effects in healthy people but based on other mammalian and primate studies its very promising. Another regimen for intermittent fasting is known as 5:2. This schedule of eating involves eating normally for five days of the week but only eating about ¼ of your normal calories for two nonconsecutive days. Alternate day fasting is pretty self-explanatory as it involves a complete day of fasting followed by an unrestricted diet the next day. One meal a day or OMAD involves eating one meal each day typically around the same time resulting in ~24 hour daily fast. This diet has recently been endorsed by Twitter CEO, Jack Dorsey (https://www.businessinsider.com/fabulous-life-of-billionaire-jack-dorsey-taking-square-public), and is the preferred diet of Dr. George Church.

Fasting produces a few other notable effects such as inducing autophagy, increased human growth hormone, reduced fasting glucose levels, reduced insulin resistance and weight loss. Autophagy (self-eating), a process by which old or misfolded proteins and components of the cell are broken down and recycled resulting in reduced inflammation. This process occurs by tagging the old proteins for delivery to the lysosome, a membrane bound organelle in Eukaryotes with an acidic environment and digestive enzymes responsible for breaking down and recycling old organelles, proteins, food, and even engulfed bacteria or viruses. Mice that are deficient in autophagy suffer from reduced lifespan, and early induction of p53 leading to premature neuron death(18). As expected, intermittent fasting is beneficial to achieving weight loss and of the 27 trials available in humans results in a 0.8% to 13.0% reduction in baseline weight without serious adverse effects(19). The studies which compared intermittent fasting to general caloric restriction found similar results. Intermittent fasting may be beneficial to patients with metabolic syndrome also known as prediabetes by improving glucometabolism. While it remains controversial whether these benefits all derive from the weight loss associated with fasting, recent human studies have shown benefits independent of weight loss including increased insulin sensitivity, and  cell responsiveness along with decreased blood pressure, oxidative stress and appetite(20). Many of these benefits are attributed to the lysosome-autophagy pathway mentioned earlier along with increases in neurogenin3, which promotes endocrine progenitors such as the beta cells in the pancreas(21).

“Whether the condition is diagnosed as a severe cold, as influenza, or as pneumonia, the first thing that should be done is to stop eating. Absolutely no food, but water, should be allowed to pass the patient’s lips until the acute symptoms have subsided. No drugs of any kind should be resorted to. Go to bed and rest. Keep warm. Rest, fasting, warmth, — these are the needs. Have plenty of fresh air in your room. Under these conditions you may lie in bed and get well in a short time with no complications and no sequels…. You don’t need treatment. The fever, inflammation, coughing, etc., constitute the healing process. Just get out of their way and permit them to complete their work. Don’t try to ‘aid nature.’ She doesn’t need your puny aid — she only asks that you cease interfering.” ~Herbert M. Shelton

Immune system deficits or over-reactivity are associated with aging and a variety of related diseases. Many promising therapies of the future involve immune modulation such as the Chimeric Antigen Receptor T-Cells (CAR-T) which reprograms the immune cells to detect a specific antigen, CD19, along with a T-cell activating protein within a single receptor. The word chimera derives from Greek mythology of a monster with a goat’s body, the tail of a serpent, and the head of a lion. Modern science has aptly used this term to describe in this case a receptor that has two dual functions. More commonly this refers to an animal that is composed of multiple different types of genetically distinct cells.

How does diet, caloric restriction and fasting relate to the immune system? This question has been studied by many researchers with promising results revealing a potential mechanism for how periods extending fasting alter the body. Unlike general caloric restriction and intermittent fasting which we have discussed so far, the next two experiments on immune function use a diet of prolonged fasting (48-120 hours). The physiological changes that occur during other types of fasting are further pronounced during prolonged fasting, but after 24-48 hours the body fully switches from the stored glycogen reserves as they are depleted and begins fat and ketone body catabolism. The body reduces pro-growth signaling and gains enhanced resistance to toxins, such as chemotherapy(22). Additionally, as the body seeks new sources of energy it increases a process known as autophagy, or self-eating, which breaks down damaged or undesirable molecules within cells and repackages them into building blocks to be recycled. This may seem stressful or damaging to cells but is in line with previous observations of hormesis, pushing the body outside its normal living conditions actually strengthens the systems of homeostasis and promotes health and longevity. Natural autophagy decreases with age which leaves room for damaged or toxic cells to accumulate and wreak havoc on normal metabolic processes.

“In a fast, the body tears down its defective parts and then builds anew when eating is resumed.” ~Herbert M. Shelton

Prolonged fasting represents a powerful mean to modulate key regulators of cellular protection and tissue regeneration but also provide a potential therapy to reverse or alleviate the immunosuppression or immunosenescence caused by chemotherapy treatment and aging, respectively. There may also be reported benefits affecting hematopoiesis, immune function, and other systems and organs (23). Prolonged fasting was also shown to benefit lymphocyte protection and alterations to hematopoietic stem cells that promote stress resistance, self-renewal and lineage balanced regeneration(23). These changes collectively boost immune function, and regeneration capacity towards a more youthful phenotype. A more recent study in mice observed a similar boost to the immune system, along with many other benefits including regulation of key proteins consoling glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function (24). This study used a dawn to dusk fasting regime and suggests that it can be a preventative therapy in cancer, metabolic syndrome, and several neuropsychiatric diseases. There is now evidence that caloric restriction promotes a healthy sleep-wake cycle, also known as circadian rhythm(25) by modulating the daily changes in leptin levels. Leptin is a hormone that regulates energy storage by inhabiting hunger and is produced primarily by adipose tissue and acts on the hypothalamus and skeletal muscles by decreasing thyroid and increasing mitochondrial efficiency respectively.

My Experience with Intermittent Fasting

When I first learned about the health and longevity benefits of caloric restriction, I considered implementing it in my own life, but I loved eating too much to make that sacrifice. It didn’t seem worth it to live in hunger without enjoying the full culinary experience. The stories of those who chose to embrace this lifestyle of reduced food intake seemed to be a bad trade in my opinion and reading their stories reaffirmed that this was similar to accepting lifelong torture and hunger for a few extra years. I wanted something that would not only extend the lifespan but extend the healthspan, the length of healthy, happy and vibrant years to your life. After years of reading about the benefits of fasting the tipping point for me was my renewed interest in resistance training and the proper diet that goes along with it. Many of my favorite personal fitness twitter personalities were endorsing the diet with apparent success and touting the psychological benefit of controlling your urges for hunger to gain mastery over the mind in other areas of your life as well. This particularly interested me due to similarities to Patanjali’s Yoga Sutra’s and its ‘science’ of the mastery of the mind. Then when one of my new co-workers in the Church lab, Raphael, told me that he was following the diet and sent along a recent review(26) I was committed and decided to try this out myself.

I jumped right into an 8-hour time restricted diet and found the transition difficult at first. My stomach would rumble, and I experienced discomfort and extreme hunger as I counted down the hours until my mid-day meal. I didn’t expect this as I would often skip breakfast but would usually have at least a snack before noon. My body was conditioned to its morning meal and tried to convert me back to my old ways. This subsided after about a week and I know now that having a glass of sparkling water limits these sensations releasing the uneasy stomach with a burp and satisfaction without any caloric intake. Even when I would skip breakfast before starting intermittent fasting, I would frequently drink a glass of chai tea latte with some milk. I found this habit the hardest to break but now I limit my milk tea drinking to the afternoon eating interval. Others have recommended black coffee in the morning to limit appetite while fasting, this may work for you, but I have always hated the taste of coffee. Others have suggested tea without sugar or milk, but this upsets my stomach when taken before food.

After a tough week of adaptation, I really began to enjoy the benefits of intermittent fasting. The first change I noticed was a ravenous appetite and increased satisfaction of eating when I would break my fast at mid-day. I started timing my weightlifting at the gym to occur right before my first meal and would consume all my protein first within the meal to stimulate the anabolic growth process right after resistance training. This totally changed my perspective on hunger and food making the protein in my meal smell and taste so delicious I would just devour it. My HDL cholesterol or good cholesterol increased ~50% after six months of intermittent fasting without increasing LDL. As I continue and adapt to this diet, I will share updates and new science as it comes along. Live long and prosper!

Other resources

https://www.hsph.harvard.edu/nutritionsource/healthy-weight/diet-reviews/intermittent-fasting/

https://www.medicalnewstoday.com/articles/327398#diabetes

https://www.forbes.com/sites/stevensalzberg/2020/01/06/can-intermittent-fasting-reset-your-immune-system/#2eb0bf8327ac

https://www.healthline.com/nutrition/intermittent-fasting-guide#benefits

P. D. Mangan (@Mangan150)

References

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First Post!

Greetings world, my name is Cory Smith and today I decided to take action and start sharing my thoughts and experiences towards attaining a vibrant, healthy mind, body and soul. Through a combination of peer reviewed research, ancient yoga wisdom and the art of mastery I will share my thoughts and experiences as I continue my personal quest for positive well-being. I’ve been researching and personally investigating this material for years and building background material and decided today was the time to share with the world.

I am in awe of the rapid revolution in technological advancement that has taken man from sharpening the first stones for basic tools into launching our probes beyond the solar system in the blink of an eye in evolutionary time. It makes me wonder how different we are from the first Homo sapiens that made rudimentary tools. We like to think we are so much more sophisticated and intelligent than them but maybe once we evolved to strike two stones together our path towards interstellar exploration was set.

I am truly grateful to be alive at such a great moment in history when we are witnessing the exponential curve of information technologies approaching their asymptotic ‘knee’ as their growth turns vertical after hundreds of thousands of years of growth that seemed linear. Follow me as I set out to share the bits of scientific research that I integrate into my personal life along with a daily yoga sadhana, or practice. My three main areas of interest that I will be writing about are science, yoga, and art.

Yoga

The word yoga derived from the Sanskrit root ‘Yuj’ meaning to yoke or bind together. The same root used for egg yolk which binds the early embryo together and provides the sustenance to mature into a vibrant healthy animal. The practice of yoga provides the practitioner with a philosophy of life and a set of physical movements that bind together the mind, body, and soul. All of yoga can be best introduced by the second line of the Yoga Sutras:

“Yoga Chitta Vritti Nirodah”
“Yoga is cessation of the fluctuations of the mind”
-Patañjali

In college I was fortunate to learn Ashtanga yoga from David Williams and vividly recall his story about seeking out a place in India where people grew more flexible and wiser as they aged, as opposed to here where the elderly became weak, fragile and decrepit. He said that Zen, meditation, yoga, they are all describing the same thing. A process to calm the mind to unnecessary distractions. Training the mind to not following the sensory stimulations that lead the mind in circles. Through the prolonged practice of yoga, it primes the body to sit comfortably and achieve a deep state of meditation. Afterwards as you go about your day distractions bring you back into fluctuations of the mind but with practice this state of peace after meditation can ultimately be extended to your entire life.

"Mind is the king of senses. One who has conquered his mind, senses, passions, thought and reason is a king among men. He is fit for Raja yoga." -B.K.S. Iyengar

When asked what yoga is, most people think of advanced pretzel like asana that only gymnasts can perform. This false impression could not be further from the truth and serves as a barrier for people to easily dismiss starting yoga by saying: “I can’t do that, I’m not flexible enough.” I’m here to tell you that you can. Yoga is not about advanced flexibility or gymnast like strength but focused on the breath and mind connection. A gymnast may be in what appears to be an advanced asana but if they are thinking about what they want for lunch or who they should meet with afterwards this person is not practicing yoga. A person with tight hamstrings who cannot touch their toes but is focused on the breath and meditation is more of a yogi than the previous gymnast. Break your expectations about what yoga is and start the practice for yourself. You can read about the theory of yoga for decades but without practice there is no advancement or true understanding.

“The mind can go in many directions in a split second. Its movements are very fast and varied. But the breath cannot go many directions at once. It has only one path: inhalation and exhalation. It can pause for a moment in a state of retention, but it cannot multiply like the mind. Controlling the breath and observing its rhythm brings the consciousness to stillness.” – BKS Iyengar

Patañjali outlined what he called the science of yoga including a path for practitioners to progress through and the distractions or obstacles of the mind (Chitta Viksepa):

1. Vyadhi – sickness which disturbs the physical equilibrium
2. Styana – languor or lack of mental disposition for work
3. Samsaya – doubt or indecision
4. Pramada – indifference or insensibility
5. Alasya – laziness
6. Avirati – sensuality, the rousing of desire when sensory objects possess the mind.
7. Bhranti Darsana – false or invalid knowledge. Illusion
8. Alabdha Bhumikatva – failure to attain continuity of thought or concentration so that reality cannot be seen.
9. Anavasthitattva – instability in holding on to concentration which has been attained after long practice.

Additional obstacles:

I. Duhka – pain or misery
II. Davrmansya -despair
III. Angamejayatva – unsteadiness of the body
IV. Svasa prasvasa – unsteady respiration

When I first read of these distractions that prevent the practitioner from doing yoga it shocked me how accurate they were having experienced them as the reasons I would stop a practice. When I experienced these distractions myself, I felt embarrassed or unsure why I was feeling and thinking these negative thoughts but pushing through these barriers is something that every yogi must go through. Knowing the roadmap with outlined potholes to avoid inspired me to train the mind to get past these weaknesses.

My path to Yoga

My first glancing experience with yoga occurred around 1997 when I was training Shotokan Karate under the guidance of Mark Linksman who occasionally taught us yoga as a complementary mind-body practice. While this experience only included a few guided sessions, it primed my muscle memory for the later yoga sessions that I would have a decade later.

In the fall of 2007, I attended an Ashtanga Yoga workshop taught by David Williams.  Through a series of postures linked by breath a rhythmic flow of energy accelerates all the particles inside every cell in your body.  The internal heat creates changes within the body.  The glands and internal organs are massaged and bathed in fully oxygenated blood, the nervous system is relaxed and revitalized.  As the heat builds unwanted toxins are burned up and excreted through perspiration. After the hour of daily practice, the body is primed for deep relaxation.  Deep relaxation has been shown to have the opposite physiological response to the fight-or-flight stress response.  The Benson-Henry Institute for Mind Body Medicine has performed a transcriptional profile to determine gene expression changes of yoga practice.  Genes involved in inflammation, the handling of free radicals, and programmed cell death.  Changes in expression of these same genes were seen in disorders such as post-traumatic stress disorder but the relaxation response changes were opposite those of the stress response.  Since that workshop I have practiced yoga typically 6 times or more per week.  I aim to incorporate yoga into personalized medicine.  After understanding how specific human variation alters physiology, are there specific yoga sequences that would be especially effective at revitalizing key areas of the body that would prevent the onset of anticipated disease? B.K.S Iyengar wrote many ‘science of yoga’ sections of his books claiming this exact thing. I believe that extraordinary claims require extraordinary evidence.

After my first Ashtanga yoga practice I was overwhelmed by the impact a single hour and a half session had on my body.  I had stumbled onto a very powerful and deeply transformative way to connect the mind, body, and soul with enthusiasm, optimism, and gratitude. I recognized immediately that this was exactly what I had been looking for to achieve a profound positive impact in regard to personal health and wellness. To be free from chronic illness and pain by attaining a vibrancy in life by persistent practice.

The life force you have extracted within the breathing, the prana. It gives a chance for the body to absorb it and to channel it throughout the entire system. You are calming the nervous system and relaxing the mind. Deep relaxation after a session of vinyasa allows every cell in your body to absorb all energy of the practice and find equipoise for the day to come. The prolonged practice of yoga brings about four characteristics that all can strive for:

1. Maitri – friendliness
2. Karuna – compassion
3. Mudita – delight
4. Upeksa – disregard

“A lamp does not flicker in a place where no wind blows; so it is with a yogi, who controls his mind, intellect and self, being absorbed in the spirit within him. When the restlessness of the mind, intellect, and self is stilled through the practice of Yoga, the yogi by the grace of the spirit within himself finds fulfillment. He knows the joy eternal which is beyond the pale of the senses which his reason cannot grasp. He abides in this reality and moves not therefrom. He has found the treasure above all others. There is nothing higher than this. He who has achieved it, shall not be moved by the greatest sorrow. This is the real meaning of yoga - a deliverance from contact with pain and sorrow.” - B.K.S. Iyengar

After years I keep coming back to this quote for inspiration and will often repeat the first line when I encounter uncertainty or fear. It reminds me that I am the flame and not the turbulent winds that surround. By setting up the right habits and continuing yoga the mind is made resilient to such stresses and does truly provide solace in troubling times. When I did my first deep dive into the yoga literature this quote, and others motivated me to deepen my practice and understanding of the philosophy behind it.

Science

Early scientific interests

I have been intrigued by the physics, chemistry and biology of heredity from an early age. I will share two childhood experiences that confirmed I was a scientist at heart. One of my earliest memories is observing a dragonfly nymph (aquatic dragonfly larvae) undergoing metamorphosis. They would crawl up on the ladder of the dock or other elevated areas to open their new wings which must dry for several minutes. During this time, they are completely vulnerable but when I was there to protect them, they were never eaten. Throughout my life I find myself repeating a quote from the movie The Fifth Element: “I must protect life.” Emerging from their old molt they begin to flutter their twin sets of wings and launch off into the air. Able to hover and dart they are aerial predators for a few weeks of flight after years of aquatic digging. I had no fear and only love for these creatures until I caught one in my hand and it bit me as hard as it could. Ouch! This early observation of how life can transform itself into something so different left me in awe of nature and with a strong desire to learn more about how life achieves such amazing feats. Richard Feynman said that the function of most biology can be ascertained by “just [looking] at the thing.”

The second early memory was the first experiment that I conducted to learn about the world around me. At a young age my first distinct memory is recalled by olfactory recognition of a blueberry muffin, our ancestral sense of smell is still the most linked to early memories. I was eating a tasty sweet blueberry crumble muffin that my mom had made on our boat on a lake in Florida. I touched the black fabric of the seat and was shocked by the heat of it. I then noticed that the white and blue sections were not as hot and conducted my own tactile experiment to confirm my initial observations. This was my first collection of experimental data that changed my view of the physical world. It stuck with me and empowered me to investigate the world around me by direct interrogation and set-up my life as a scientist.

Reading DNA

The molecular instructions for life are encoded in a carbon-based polymer known as deoxyribonucleic acid (DNA). The sum DNA of a single cell is referred to as the genome of an organism and contains the fractal instructions in 2D (linear sequence of nucleotides) that is ultimately translated into an amino acid sequence that folds into a 3D structure known as a protein. The word protein derives from the Greek word proteios meaning primary or holding first place as these molecules compose the most mass in living organism (dry mass). Through this compression of information into a linear sequence life can pass on its instructions to the next generation. We live in an exciting era of time when the person who first discovered “the molecular structure of nucleic acids and its significance for information transfer in living material" is still alive and was one of the first people to have their whole genome sequenced (James Watson).

I took my passion for genetics and heredity into my University studies majoring in Microbiology and Cell Science at the University of Florida. Learning about the molecular and technological process of DNA sequencing fascinated me and I knew I wanted to learn as much as I could and master the techniques to sequence DNA with my own hands. I was heavily influenced by two great professors at the University of Florida, Dr. Eric Triplett and Dr. Bill Farmerie, who taught a class on DNA sequencing that included a hands-on tutorial on how to do it ourselves, and analyze the results. This was the era of so-called ‘Next Generation Sequencing’ (NGS) that dramatically reduced the cost of genomics making it available to nearly all research labs around the world opening up the promise of personalized medicine to tailor individual treatment towards their specific genetic predispositions as opposed to the average individual. While some diseases are caused by a single base change in DNA, most disease is complex including many genetic variants and are influenced by interactions with the environment.

Writing DNA

Now that we can read DNA the next obvious step is to learn to write DNA. Rudimentary forms of DNA manipulation were first developed in the 1970s using a set of enzymes known as restriction endonucleases. These tools allowed researched to cut and paste DNA leading the first recombinant DNA and allowing for medical advancements such as the isolation and production of insulin for patients with diabetes. With this basic ability to alter existing DNA scientists could clone genes into viral vectors and got way ahead of themselves pushing human trials in the 1990’s. After a series of failures including the death of Jesse Gelsinger who suffered from ornithine transcarbamylase deficiency. After receiving a viral vector-based therapy to restore this broken gene he died four days later after a massive immune response to virus leading to multiple organ failure. These first-generation human gene therapies were put on hold for more than a decade to develop more precise means of genetic alteration that don’t integrate randomly into the genome or cause a severe immune reaction.

A revolution in DNA editing occurred when scientists revealed a method to precisely modify DNA in nearly any organism based on a bacterial immune system known as Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR. In nature bacteria encode this DNA targeting and cutting enzyme to build up a repertoire of invasive virus’s that can be destroyed selectively based on their DNA sequence. Many people report that scientists ‘invented’ this technology, but they merely discovered a natural system and adapted it towards biotechnology applications. This simple tool allows researchers to alter their gene of interest in a way that was previously not within their budget or technical capacity. After billions of years of experience nature and life truly are grand engineers. But are they a blind watchmaker as described by Richard Dawkins?

During my time in graduate school (2010-2015) I witnessed the CRISPR revolution and was able to apply these technologies in human stem cells to better model hematological disease and better define the off-target risk of these technologies. Now in the Church lab I am working on Genome Project Write to further develop large-scale genome editing technologies to allow for the safe editing of thousands of loci to allow for the radical redesign of mammalian genomes.

Anti-aging research

A story I grew up with in Florida is the quest for immortality by seeking the ‘fountain of youth.’ I visited this historic site in St. Augustine Florida as part of an elementary school field trip and was told the story about Ponce de Leon and his search for a mysterious fountain that was rumored to extend life and possibly bring about immortality. The ultimate goal of the ego is to prolong its existence which has long been desired by many great men and women throughout history. Most people want to live a long and healthy life but setting the habits to accomplish this seem out of reach. You’ve all heard this before and will probably ignore again but we have known for quite a while what common habits are associated with a vibrant life of longevity. How can we encourage our society to better implement these behaviors and make them accessible to all.

• Community
• Enjoyment
• Friends and loved ones
• Satisfaction with what you do for a living
• Eating a healthy diet
• Exercising regularly
• Meditation
• Not drinking too much alcohol
• Not smoking

In future posts I will review the science of aging research and share my experience implementing what

1. Caloric restriction
2. Intermittent fasting
3. heterochronic parabiosis
4. Sirtuin activating compounds
5. Pluripotent stem cells

Art

Scientific research is perceived as unapproachable to the majority of the population due to its complex jargon and unrelatable subfields that seem like gibberish to the general population. I strive to make my research relatable to all levels of experience and practice this skill talking with my grandmother, taxi drivers and other random people I encounter. Through this process I found that most people are very interested in these topics and want to learn more. The intersection of art and science speaks in universally understood language of beauty. In addition to what is classically thought of as art I include ancient texts such as the Book of Five Rings and modern science fiction.

Ancient wisdom

A Book of Five Rings is written on the art of mastery and a no-nonsense direct style that through his direct experience of mastering the sword and dueling teaches one to apply this knowledge to the rest of your life. Miyamoto Musashi was a Japanese samurai that was undefeated in his 61 duals noted for his dual bladed technique then writing his philosophy including A Book of Five Rings. Earth, Water, Fire, Wind and Void are the five rings composing this book and each teaching the basics of life which apply to 1, 10, and 10,000. This book relates his experience of combat sword fighting to mastery of all skills in a way that appeals to modern businessmen, and academics.

The I-Ching, or the book of changes is an ancient Chinese text that outlines a divination practice to provide guidance on questions asked. It involves a process known as cleromancy, the use of random number generation to create a set of hexagrams pointing towards the relevant text to answer your question. It is one of the oldest Chinese classics that was modified over the years by philosophers including Confucius who added the Ten Wings commentary to the original text. During my early Shotokan training I was introduced to this text and have consulted it for many important decisions throughout my life. By asking a question and receiving universally sound advice your mind can have confidence that you are taking the correct path, removing indecisiveness and uncertainty from the decision.

Science Fiction

Many scientific advancements have first been imagined by writers who shared their thoughts with the world. Although they did not know the means to manifest these technologies, by releasing the idea out into the collective consciousness others with the means begin working towards making it a reality. A relevant example in our daily lives now is the early appearance of smart phone like devices in Dick Tracey's wristwatch, a two way communicator with many of the functions we all now carry around in our pockets. Another great example of this is the author Arthur C Clark of classics like 2001 A Space Odyssey who correctly predicted the following in his stories:

1. Communication satellites
2. Asteroid of interstellar origin
3. Artificial intelligence
4. Landing on a comet
5. Gravity assist maneuver

Last year I started a mindfulness practice I call my ‘read ledger’ to record the books I have read, how long it took me and a list I plan to read in the future. Shortly after doing this I built my future read list with over 100 books I wanted to experience next. I aim to build a community to read these stories together and discuss the implications for current science and identify how these imagined future technologies can be brought into reality. Here is a link to my personal Read ledger if you want to use it as a template for your own log or read along with our virtual community. I've also included what I call the Science Fiction Compendium to select future books I want to read and build up this list by finding those with shared interests. I have been inspired by Isaac Arthur who runs the YouTube channel Science and Futurism by Isaac Arthur where he discusses science and futurism often inspired by science fiction. Thanks for reading until the end and I look forward to contributing to this niche of the internet sharing my experience with yoga, science and art.