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Disclaimer:  This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on literature review at the time of the blog and may change as new evidence evolves.

Major In The Majors

The #1 Thing You Can Do for Your Health

There was nothing about Jeanne Louise Calment that stood out as remarkable. She was born in Arles, France, in 1875, a year before Alexander Graham Bell patented the telephone. She had a normal childhood. At age 21, she married a well-to-do man who allowed her to live a carefree life without work. She loved the outdoors and led a lifestyle of active leisure. She ate the typical whole-food diet of rural France in the early 20th century. She loved dark chocolate. After her evening meal, she enjoyed a glass or two of port wine. Her husband introduced her to smoking when she was 21, and she smoked one or two cigarettes a day, usually after dinner. Indeed, nothing about Jenne’s life seems out of the ordinary.

What was extraordinary about Jeanne Louise Calment was that she lived to be 122 – the longest verified human lifespan in history.

To put that in perspective, only 1 out of 6000 will live to be 100. One out of every 7 million will live to be 110. But Calment defied all the odds – out of the billions and billions of lifespans ever recorded, she beat them all, not by a small amount.

To be sure, she didn’t live a lifestyle that most health experts would describe as perfect. She started smoking when she was 21 and quit when she was 117. She drank alcohol and ate sweets – although in moderation. She couldn't access modern purported longevity compounds like metformin or rapamycin.

Jeanne’s exceptional longevity raises an interesting question: What variables matter the most to health and longevity? Genetics alone can't explain her long lifespan – careful research has shown that genetics only accounts for 20% of our health and longevity. Jeanne’s parents and siblings lived long lives, but not remarkably so.

Majoring in the "Majors"

Research has demonstrated that simply getting the "major" lifestyle factors right can dramatically influence our health. For example, a study published in the Journal of the American Medical Association concluded that four healthy lifestyle factors -- never smoking, maintaining a healthy weight, exercising regularly, and following a healthy diet -- together appear to be associated with as much as an 80 percent reduction in the risk of developing the most common and deadly chronic diseases(1).

Never smoking, maintaining a healthy weight and regular exercise are self-explanatory. However, the composition of a “healthy diet” remains controversial. One “major” dietary rule where there is consensus is eating whole foods and avoiding processed foods. Following this simple rule will allow you to extract the significant benefit of a healthy diet. Indeed, Calment's diet reflected the wonderfully rich cuisine in late 19th/early 20th century France – a diverse spectrum of whole-food ingredients and wild game.

Calment ticked off all the other "major" healthy-lifestyle factors – she maintained a healthy weight, got plenty of exercise, and lived an exceptionally stress-free life.

Where she failed, however, was in never-smoking.

How, one might ask, could Calment have lived the most extended lifespan ever recorded yet have violated one of the most essential health rules?

When bad things become good and then bad again: the curious phenomenon of hormesis

One explanation could be the fascinating biological dictum of hormesis. Simply put, hormesis is the natural response curve to stressors and toxins (things that stress the body).

Curiously, stressors, at low doses, stimulate a biological process that increases the health and fitness of an organism. A complete absence of stressors or to many stressors inhibits these health-imparting biological processes.

The list of agents that induce a hormetic response can be surprising and counterintuitive, including toxic agents like ethanol, carbon monoxide, and radiation. A poignant real-world example of the hormetic effect occurred when recycled radio-isotope-contaminated steel was inadvertently used to construct a series of apartment buildings in Taiwan. The result was that 10,000 people were exposed to an average dose rate of 50 mSv/year of radiation, with 1,000 of the 10,000 residents receiving a larger dose, amounting to over 4,000 mSv over ten years in one particularly contaminated building.

When it was later learned that the buildings were contaminated, researchers seized the opportunity to study the effects of long-term radiation exposure on cancer rates. In the general Taiwanese population – based on the known death rate of spontaneous cancers at the time – 232 people would be expected to die from cancer out of a population of 10,000. According to everything known about the effects of radiation on the human body, the cancer deaths in the radiation-exposed buildings were expected to produce 70 excess deaths over the average cancer death rate of 232, for a total of 302 cancer deaths in the 10,000 exposed residents.

Stunningly, only 7 of the exposed residents developed cancer -- about 3 percent of spontaneous cancer death in the general Taiwan public! The consensus explanation for this strange observation from experts is that the radiation exposure landed in the “beneficial” range of the hormetic curve(2).

Even exercise (a stressor) adheres to the hormetic dose-response curve. Studies have shown that zero activity is harmful to our health and too much exercise can also be detrimental(3).

Jeanne Calment
Jeanne Calment

For Calment, perhaps her "bad" lifestyle habits – the after-dinner glass of port wine and cigarette – may have conferred a hormetic effect.

(No health experts I know, including myself, would ever advocate exposing oneself to radiation or smoking to achieve hormesis. Instead, hormesis is best achieved through stressors like exercise, fasting, heat and cold exposures, and more)

The Invisible Shield for Long Life

In addition to the “major” lifestyle variables we've discussed, exciting new research has identified one that stands above the rest: your social life.

Julianne Holt-Lunstad, a researcher in the phycology department at Brigum Young University, observed that people with strong social connections had an invisible internal shield that blunted the physiological response to stressful situations. In lonely individuals, she documented that stress-induced caustic hormones spill into the bloodstream, raising blood pressure and promoting inflammation. Conversely, these hormones were released to a much lesser degree in people with strong social connections. Inspired by this observation, Holt-Lunstad then painstakingly sifted through the records of over 3 million people and determined that close relationships and social integration (the number of positive contacts you have with people throughout your day) had by far the most significant impact on health, even more than excessive drinking, smoking, diet, and exercise.

How can intangible factors like close relationships and social integration affect our health more than tangible factors like diet, exercise, obesity, and smoking? The new science of social genomics suggests that the answer lies in a biological loop that knits the neurological inputs generated from interacting with people into a deeply complex cellular response that occurs at the epigenome level.

The changes in the epigenome from social interaction center on the immune system. Researchers analyzed the genes in white blood cells in healthy adults that reported different levels of loneliness. Among the 22,283 genes analyzed, 209 showed a significant difference in expression levels in lonely subjects compared to those with strong social connectedness. A striking pattern emerged when the researchers analyzed the 209 differentially expressed genes. "These effects did not involve a random smattering of all human genes, but focally impacted three specific groups of genes. Genes supporting the early ‘accelerator’ phase of the immune response – inflammation – were selectively upregulated. However, two groups of genes involved in the subsequent ‘steering’ of immune responses were downregulated.” In other words, the lonely subjects' immune systems were more prone to deleterious inflammatory responses and less able to mount a targeted response to infection(4).

“These results provided a molecular framework for understanding why socially isolated individuals show heightened vulnerability to inflammation-driven cardiovascular diseases and impaired responses to viral infections and vaccines,” noted one of the authors of the study.

Strong social connectivity is one explanation for Jeanne Calment’s exceptionally long life. She spent days with others playing tennis, fencing, attending the opera, swimming, and even accompanying her husband on hunting parties. On her 100th birthday, she rode her bike around her village and thanked everybody for wishing her a happy birthday. Reports on her life suggest that she maintained social connectivity into her old age. After fracturing her hip at age 112 (from which she fully recovered), she moved into a nursing home where she befriended one of the nurses, and together they would share an after-dinner cigarette. In the evenings, she enjoyed going from room to room, talking with the other residents about the current events she had learned that day.

Jeanne Calment
Jeanne Calment

One additional distinguishing feature of Calment seemed to have been her steadiness, she rarely appeared to be stressed about anything. “I think she was someone who, constitutionally and biologically speaking, was immune to stress,” said one of her close friends.

A Healthy Life is a Meaningful Life

The lessons we can learn from Jeanne Calment and the science of longevity are numerous: If we get the "major" things right, like not smoking, a good diet, quality sleep, exercise, and, critically, connections to people, then there is little else to worry about. The fact that our body's response to stress tracks a hormetic curve guides us to the realization that we don't have to get everything perfect to achieve optimal health – small amounts of “bad” things can even be reasonable under the right circumstances. Indeed, the lessons from Jeanne Calment’s life and the recent research on social genomics shows us that a meaningful life–one rich with social connectivity–is perhaps the most important thing you can do for your overall health.

Let Meakin Metabolic Care get your Major Things Right

At Meakin Metabolic Clinic we major in the majors. Our MOP program is carefully designed around getting the big things right in order to achieve the longest and healthiest lifespan for our clients. The core lab work is centered around identifying the most actionable markers of inflammation and metabolic optimization. We then work with you to bring these critically important markers into the optimal range. With the C-MOP program, we further optimize the “Majors” in cancer patients during or following cancer treatments and use repurposed drugs to intensify the impacts. We offer these and other services in a convenient virtual, low-cost manner and cover 45 states. Please check out our home page below.

Stay Curious and be your own Best Doctor,

Charles Meakin MD, MS, MHA

Travis Christofferson MS

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.


1 Earl S. Ford; Manuela M. Bergmann; Janine Kroger; Anja Schienkiewitz; Cornelia Weikert; Heiner Boeing. Healthy Living Is the Best Revenge: Findings From the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. Arch Intern Med., 2009

2 Chen WL, Luan YC, Shieh MC, Chen ST, Kung HT, Soong KL, Yeh YC, Chou TS, Mong SH, Wu JT, Sun CP, Deng WP, Wu MF, Shen ML. Effects of cobalt-60 exposure on health of Taiwan residents suggest new approach needed in radiation protection. Dose Response. 2006 Aug 25;5(1):63-75. doi: 10.2203/dose-response.06-105.Chen. PMID: 18648557; PMCID: PMC2477708.

3 Laddu DR, Rana JS, Murillo R, Sorel ME, Quesenberry CP Jr, Allen NB, Gabriel KP, Carnethon MR, Liu K, Reis JP, Lloyd-Jones D, Carr JJ, Sidney S. 25-Year Physical Activity Trajectories and Development of Subclinical Coronary Artery Disease as Measured by Coronary Artery Calcium: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Mayo Clin Proc. 2017 Nov;92(11):1660-1670. doi: 10.1016/j.mayocp.2017.07.016. Epub 2017 Oct 16. PMID: 29050797; PMCID: PMC5679779.

4 Cole SW, Hawkley LC, Arevalo JM, Sung CY, Rose RM, Cacioppo JT. Social regulation of gene expression in human leukocytes. Genome Biol. 2007;8(9):R189. doi: 10.1186/gb-2007-8-9-r189. PMID: 17854483; PMCID: PMC2375027.


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