Legend has it that one of the greatest fears of Mithridates VI, King of the Hellenistic State of Pontus, was being poisoned by his enemies, as his brother, Mithridates V, had been. To prevent the same thing from happening to him, the king took young people small doses of different poisons with the idea of immunizing themselves against them. What Mithridates did not know was that, over time, this immunization would cause problems.
According to the Roman historian Appian in his book Roman History, when the Hellenic king was defeated by Pompey, he wanted to commit suicide to avoid a humiliating capture. The poison, due to his “training”, did not work and to carry out his objective he had to ask one of his officers to pierce him with a sword.
Whether this legend is true or not, the truth is that what happened to Mithridates really has a scientific basis. It is a biological process called hormesis and which, as we see, has been known for centuries. It has been in recent times that science has set out to take advantage of its potential seriously, trying to use it to solve problems in our body, one of the most interesting of which is aging.
“Hormesis is a biological process by which a cell or a group of cells responds adaptively to an external factor or agent that would be harmful at high doses, but not at controlled doses that manage to avoid this damage and instead achieve a beneficial effect for the body,” explains Dr. Carlos Gutiérrez, specialist in Family and Community Medicine, expert in Genomic Medicine and genetic counseling (EADE) and in Longevity Medicine, as well as Medical Director of Actiage Anti-Aging. “In simple terms, hormesis suggests that small doses of something potentially harmful can be not only safe, but also beneficial, since they can stimulate the body to develop cellular defense and repair mechanisms. As they say: 'what doesn't kill you makes you stronger.'"
“To better understand the definition,” adds Dr. Jonathan Franco, Meditelier Internal Medicine specialist at Clínica Mi Tres Torres, “imagine that your body is like a warrior that gets stronger by facing challenges. Hormesis is precisely that, a biological process where controlled exposure to low doses of stress or harmful agents of all kinds activate adaptive responses that strengthen the organism, thus improving its ability to resist diseases and, also very interesting, to reverse the signs. of aging.”
It is on hormesis that the benefits of saunas, cold showers, intermittent fasting and even physical exercise are based, although, as we will see, their application and benefits can also be more complex. According to Dr. Franco, “the benefits of hormesis are diverse and very evident in health. From strengthening the immune system to improving cognitive or circulatory function, through its action to combat the aging of cells that usually occurs as we age and causes some organs to deteriorate."
According to the doctor, the underlying biological mechanisms that explain the protective effects of hormesis are complex and fascinating. From activating antioxidant enzymes to improving mitochondrial function, hormesis works at the cellular level to strengthen the body and protect it against oxidative damage and inflammation, two key processes in aging and the development of chronic diseases.
Currently, hormesis is already being applied in medicine to treat and prevent a wide variety of diseases. According to Dr. Gutiérrez, its most common uses are the following:
●Radiotherapy. In cancer treatment, radiation therapy uses ionizing radiation to destroy cancer cells. The idea of hormesis is applied by adjusting radiation doses to maximize damage to cancer cells while minimizing damage to surrounding healthy cells. There have been studies exploring how low doses of radiation could have stimulatory effects on normal cells, protecting them or making them more resistant to future damage.
●Immunotherapy. Some forms of immunotherapy reflect principles of hormesis. In them, small doses of immunological agents or allergens are administered to “train” the immune system to respond more effectively or to desensitize the body against specific allergies.
●Treatment of neurodegenerative diseases. In diseases such as Alzheimer's or Parkinson's, research is being carried out on how induced stress, such as mild heat or controlled oxidative stress, can activate cellular responses that protect or repair neurons.
●Heat and cryotherapy. Therapies that involve exposure to heat (such as saunas) or cold (cryotherapy) use the principle of hormesis by inducing controlled stress on the body. These practices can improve circulation, reduce inflammation, and stimulate the immune response.
●Treatments used in aesthetic medicine. Many of them produce controlled damage to the skin that stimulates skin repair mechanisms, favoring the differentiation of fibroblasts and stem cells to produce new cells in the dermis.
If we talk about preventing aging, Dr. Gutiérrez points out oxidative stress as one of the great hormetic tools. “Most hormetic stressors generate low levels of free radicals in the body,” he says. “This may seem bad, but it is actually not, since our mitochondria, which are responsible for producing the energy our cells need to function, generate more copies of themselves in the presence of certain free radicals. As we age, we lose mitochondria—in fact, it's a hallmark of aging—which can leave us tired and without the energy to optimally fuel cellular processes. By stimulating mitochondrial biogenesis, both short- and long-term health can be improved.”
Among the interventions accepted to reduce or delay aging, the doctor highlights caloric restriction, dietary restriction (or intermittent fasting), pharmacological interventions and exercise. All these actions accelerate the metabolism of the mitochondria and the moderate formation of ROS (Reactive Oxygen Species) that increase resistance to stress, antioxidant defense and increase longevity.
Caloric restriction, for example, which involves reducing daily caloric intake without causing malnutrition, has been shown to increase longevity in various animal studies. “Caloric restriction is believed to induce hormesis by increasing cellular activity and reducing oxidative damage, which could prevent or delay age-related diseases,” explains Gutiérrez. “Calorie restriction involves reducing the daily amount of calories between 10 and 40%, although it depends on each person, ensuring the necessary intake of nutrients to maintain our health. This restriction must also be carried out indefinitely, but periods of higher intake could be cycled to avoid the loss of muscle mass.”
Intermittent fasting puts our body in a state of stress due to temporary nutrient deprivation, triggering a cellular cleansing process known as autophagy, which can contribute to better cellular health and longevity. “The type of fasting we choose will depend on various factors, but it does not necessarily have to be too intense to obtain benefits,” says the doctor. “Just limiting your eating to a period of eight or ten hours, for example, eating 10 to 20 hours a day, can be beneficial for your health.”
High-intensity interval training, known as HIIT, characterized by intermittent bursts of maximum effort for about 30 seconds followed by 15 seconds of rest, is one of the most efficient ways to experience hormesis. “During these intense bursts, the muscles briefly lack oxygen (hypoxia), which stimulates the production of mitochondria. You're also activating fast-twitch muscles, which can be beneficial for longevity. Any exercise that challenges you, whether it's an intense spinning class or boxing training, is a good option,” says Gutiérrez.
Saunas, hot baths, exercising on a warm day, or even taking a hot yoga class are ways to reap the benefits of heat. According to the doctor, sauna use, specifically, has been associated with a reduced risk of mortality from all causes; and periodic exposure to heat, in general, can increase the expression of “heat shock” proteins in the body, which can help strengthen the immune system and promote longevity.
Ice baths, cold showers, or even spending time outdoors in cold weather can also be beneficial. “Regular exposure to cold has been shown to increase levels of certain immune cells, including cytotoxic T cells, which play a role in eliminating virus-infected cells and cancer cells,” says the doctor, “and can significantly increase the life expectancy of certain animals. “Both heat and cold exposure have also been associated with mitochondrial biogenesis.”
Hormesis has some associated risks. Dr. Franco uses precisely this argument to highlight an idea: that each body is different. Therefore, it is necessary, according to him, for a professional to individually and comprehensively evaluate the health of each patient, “it would be the best option to prevent complications,” he says.
Among the most important risks that the doctor points out are the following:
●Excessive exposure to stress: supplements or intense exercise can cause cell damage.
●Nutritional deficiency: With calorie restriction and intermittent fasting, some bodies may absorb fewer vitamins and minerals essential for health.
●Muscle injuries: mainly in intense physical activities.
●Psychological impact: some measures can trigger eating disorders or body image problems.
●Interactions with other drugs: in the case of patients who take medications or already have a disease.
And what does the future look like? Will there be more applications and therefore more benefits of hormesis in the coming years? Dr. Franco assures us that today there is numerous research underway with the aim of taking advantage of this biological process to treat some of the most complex diseases we face. Some examples are:
●Neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS (amyotrophic lateral sclerosis). Patients with these pathologies are being administered phytochemicals, increasing their physical activity and applying brain stimulation to improve neuronal function and reduce the risk of cognitive decline.
●Anti-aging. Supplements and vitamins at high doses are being investigated to achieve antioxidant effects, as well as medications that influence telomeres, which are special DNA sequences found at the ends of chromosomes and which are directly related to aging. .
●Metabolism and cardiovascular health. The impact of calorie restriction, physical exercise and the administration of phytochemicals in patients with type 2 diabetes mellitus and myocardial infarction is being investigated.
●Cancer. Research is underway to investigate how hormetic agents such as physical activity and supplements can inhibit tumor growth, promote apoptosis (cell death) of cancer cells, and improve the effectiveness of chemotherapy and radiotherapy.
In short, hormesis is destined to play a very important role in preventive and anti-aging medicine of the future, so soon we will all be more familiar with it and its treatments.
