Chronological age and biological age
Chronological age is an objective measure: it increases progressively as the years pass. Biological age, on the other hand, attempts to describe how functionally young or old our organism appears compared to our chronological age.
Two people of the same age can, in fact, have very different metabolic, cardiovascular, muscular, and immune conditions. The difference depends on the interaction of numerous factors: diet, physical activity, sleep quality, stress, body composition, metabolism, environmental exposure, and behavioral habits.
Biological age is therefore not a single, unchanging number. It is an indirect representation of the organism's state, obtained through various physiological and molecular markers.
This concept is particularly interesting in aging research because it shifts the focus from the simple passage of time to the speed at which the organism accumulates age-related alterations. In the source material, for example, biological age is linked to parameters such as cardiovascular function, muscle strength, bone density, hormones, and other physiological indicators.
The environment and oxidative stress
The organism is continuously subjected to stimuli from the external environment and internal metabolism. Air pollution, particulate matter, smoke, alcohol, certain chemicals, an unbalanced diet, and other factors can contribute to increased oxidative stress.
Oxidative stress occurs when the production of reactive oxygen and nitrogen species exceeds, under certain conditions, the ability of cellular systems to neutralize them and repair the damage.
The phenomenon should not be interpreted simply as the presence of “free radicals” to be eliminated. Reactive species also have physiological functions in cell signaling and the immune response. The problem arises especially when the redox balance is persistently altered.
Over time, chronic oxidative imbalance can contribute to damage to lipids, proteins, and nucleic acids, and interact with other fundamental aging processes, including mitochondrial dysfunction, chronic inflammation, epigenetic alterations, and cellular senescence.
The source text identifies the environment, smoke, alcohol, exposure to chemicals, and diet as some of the main factors capable of increasing the oxidative load.
Diet and antioxidant defenses
Diet represents one of the main tools through which to modulate metabolism and provide the organism with micronutrients and bioactive compounds.
Fruit, vegetables, legumes, whole grains, nuts, seeds, spices, aromatic herbs, and extra virgin olive oil provide a wide variety of bioactive molecules, including vitamin C, vitamin E, carotenoids, and polyphenols.
However, it is not correct to consider foods exclusively as simple “containers of antioxidants.” Their biological effect derives from the interaction between fiber, micronutrients, polyphenols, fatty acids, microbial metabolism, and the organism's response.
For this reason, in the context of healthy aging, the overall dietary pattern takes on greater importance than the search for a single food or a single molecule.
The source material also proposes a diet characterized by a high presence of plant-based foods, whole grains, legumes, spices, aromatic herbs, and extra virgin olive oil.
The fasting-mimicking diet and biological age
Among the nutritional interventions that have attracted the most interest in the field of longevity is the fasting-mimicking diet, or FMD.
It is a short-term dietary protocol, generally structured in five-day cycles, characterized by reduced calorie intake, a relatively high proportion of unsaturated fats, and a reduction in protein and sugar, followed by a return to regular eating.
The goal is not simply to reduce calories, but to create metabolic conditions for a limited period that reproduce some aspects of the physiological response to fasting, without resorting to complete water fasting.
The source material describes exactly this model as a five-day hypocaloric intervention, followed by refeeding periods.
The most interesting clinical research in relation to biological age was published in 2024 in Nature Communications. The analysis considered participants from two clinical studies and evaluated the effects of three cycles of the fasting-mimicking diet on various metabolic and biological markers.
After three cycles, researchers observed a median reduction in estimated biological age of about 2.5 years, along with favorable changes in some metabolic markers, hepatic fat content, and the lymphocyte/myeloid ratio. The effects were also observed in a second clinical cohort.
However, it is important to interpret this result correctly: a reduction in estimated biological age does not prove that a person has actually “rejuvenated” by 2.5 years or that they have automatically increased their life expectancy. It is a variation obtained through biomarkers associated with aging.
This distinction is essential when talking about longevity.
Metabolism, visceral fat, and insulin sensitivity
The effects observed in the studies on the fasting-mimicking diet mainly affect the metabolic area.
In the first randomized clinical study on FMD, three monthly five-day cycles were associated with a reduction in body weight, trunk fat, and total body fat, as well as a decrease in blood pressure and IGF-1. The improvements in some risk factors were particularly evident in subjects who initially had more unfavorable values.
The subsequent analysis published in 2024 also highlighted a reduction in insulin resistance and liver fat, along with changes in markers used to estimate biological age.
These results suggest that one of the ways FMD may influence aging-related processes is through the improvement of the metabolic profile.
Persistent alteration of insulin sensitivity, the accumulation of visceral and liver fat, and metabolic inflammation are indeed conditions closely linked to cardiometabolic health and the progression of numerous chronic processes.
The immune system and aging
Aging also affects the immune system. Over the years, changes occur in the composition and functionality of immune cell populations, a phenomenon collectively referred to as immunosenescence.
In the study on the fasting-mimicking diet, an increase in the ratio between lymphoid and myeloid cells was observed, interpreted by the authors as a possible indicator of a biologically younger immune profile.
This is an interesting finding because it suggests that the effects of nutrition are not necessarily confined to energy metabolism.
The relationship between metabolism, the immune system, and aging is, in fact, increasingly studied in the field of immunometabolism: nutrients, insulin, growth factors, inflammation, and cellular signals can interact, modifying the organism's response over time.
However, in this case too, it is more correct to speak of a modification of biomarkers associated with immunological age rather than a true “rejuvenation” of the immune system.
Fasting, autophagy, and regeneration: what we know
One of the reasons fasting and the fasting-mimicking diet are studied in the context of longevity concerns the ability of nutritional restriction to modify numerous metabolic pathways.
During periods of reduced energy availability, signals related to insulin, IGF-1, mTOR, AMPK, and mitochondrial metabolism change, among others. In experimental models, these changes can promote cellular adaptation and recycling processes, including autophagy.
The fasting-refeeding sequence is particularly interesting because the two phases can have different biological functions: the first promotes adaptation and cellular recycling signals, while the latter provides the energy and substrates necessary for rebuilding processes.
In the source material, this concept is described as alternating between restriction cycles and refeeding periods, with the goal of promoting the elimination of damaged cellular components and subsequent regenerative processes.
However, it is important to distinguish the results obtained in model organisms from the evidence available in humans. The idea of “cellular regeneration” is biologically plausible and supported by numerous experimental studies, but it cannot be automatically translated into the statement that one cycle of FMD regenerates organs or tissues in humans.
The daily diet between one cycle and the next
The fasting-mimicking diet should not be interpreted as a shortcut capable of compensating for an unfavorable lifestyle.
Metabolic health and aging are the result of cumulative exposure to numerous factors. For this reason, between one FMD cycle and the next, the quality of the daily diet remains fundamental.
A diet oriented toward longevity should especially favor minimally processed plant-based foods, fiber, legumes, whole grains, fruit and vegetables, adequate sources of unsaturated fats, and an appropriate amount of protein.
The source text proposes grains such as brown rice, farro, barley, oats, millet, teff, and quinoa, along with legumes, plant-based foods, spices, aromatic herbs, and extra virgin olive oil.
The central point is not to create a rigid list of “anti-aging” foods, but to create a diet that is overall favorable to metabolic health.
Fewer ultra-processed foods, more dietary biodiversity
A long-term health-oriented nutritional strategy should reduce the presence of energy-dense, low-nutrient foods, especially when they systematically replace fiber- and micronutrient-rich plant-based foods.
Variety is equally important.
Different colored vegetables, legumes, whole grains, fruit, seeds, nuts, aromatic herbs, and spices provide different combinations of fiber and bioactive compounds that also interact with the intestinal microbiota.
In this sense, diet can be considered not only as a source of energy and micronutrients, but as a system of metabolic signals capable of communicating with the organism and the intestinal microbial community.
The meal as a metabolic behavior
The quality of the diet does not depend exclusively on the chemical composition of the foods.
Eating behavior can also contribute to health: eating slowly, chewing properly, avoiding eating meals under stress, and maintaining regular hydration are simple habits that can promote a better eating experience.
The source material places particular importance on slow and mindful chewing, describing the meal as a time to reduce distractions and pay attention to flavors and aromas.
These behaviors should not be presented as tools capable on their own of “rejuvenating” the organism, but can be integrated into an overall health-oriented lifestyle.
Fermented foods, spices, and plant-based foods
A varied diet can also include fermented foods such as yogurt, kefir, sauerkraut, fermented vegetables, miso, and tempeh.
Research on the microbiota is increasingly studying the possible role of dietary diversity and fermented products in modulating the intestinal ecosystem and immunometabolic signals.
Spices and aromatic herbs can also increase the variety of bioactive compounds introduced through the diet. Basil, oregano, ginger, thyme, cinnamon, rosemary, cumin, coriander, turmeric, garlic, and other aromatic plants can contribute to the phytochemical complexity of the diet.
The fundamental principle remains, however, variety, not the search for a single miracle substance.
Extra virgin olive oil and dietary pattern
Extra virgin olive oil represents one of the main sources of unsaturated fats in the Mediterranean tradition and contains numerous phenolic compounds.
Its inclusion in a dietary pattern rich in plant-based foods, legumes, whole grains, fruit, fish, and nuts is consistent with the dietary patterns most studied for cardiovascular and metabolic health.
The source material also emphasizes the importance of extra virgin olive oil, preferably used raw and stored correctly.
And red wine?
Red wine is often associated with the concept of antioxidants and the presence of polyphenols, particularly resveratrol.
This does not mean, however, that alcohol consumption should be recommended to obtain longevity benefits. Alcohol is associated with health risks, and the polyphenol content of wine does not cancel out these risks.
For this reason, in the context of a diet oriented toward healthy aging, it is preferable to obtain polyphenols from grapes, berries, vegetables, unsweetened cocoa, tea, and other plant-based foods rather than using wine as a preventive tool.
The fasting-mimicking diet is not a do-it-yourself practice
FMD research is promising, but this does not mean that the protocol is suitable for everyone.
The available clinical studies are still relatively limited compared to the complexity of human aging and do not show that the fasting-mimicking diet automatically prevents or treats cancer, diabetes, cardiovascular or neurodegenerative diseases.
Furthermore, a hypocaloric protocol concentrated in a few days may require particular attention in frail, elderly, underweight people, or those with metabolic or clinical conditions that require pharmacological therapy.
For this reason, any fasting or fasting-mimicking diet protocols should be personalized and supervised by a qualified professional, especially when diseases or pharmacological therapies are present.
The source material also emphasizes that the personalized application of the longevity diet and the fasting-mimicking diet requires professional expertise and that doing it yourself can involve risks.
A New Perspective on Aging
Interest in biological age stems from a simple but profound question: can we change the speed at which our bodies age?
Contemporary research suggests that aging is not a completely rigid process. Metabolism, inflammation, body composition, physical activity, sleep, stress, diet, and environment continuously interact with cellular processes.
The fasting-mimicking diet represents one of the most interesting nutritional approaches in this field. The available clinical studies have shown favorable changes in several metabolic biomarkers and, in the 2024 study, a reduction in estimated biological age of about 2.5 years after three cycles.
Other more recent clinical studies are continuing to evaluate the effects of periodic FMD cycles on cardiometabolic and functional parameters. A randomized trial published in 2023, for example, compared four monthly cycles of FMD with a continuous Mediterranean diet in overweight/obese people with hypertension, highlighting the need to carefully evaluate the vascular effects of the different protocols as well.
These results do not yet authorize us to speak of an “elixir of life.” However, they indicate an important research direction: intervening in the metabolic processes that accompany aging could become a component of longevity medicine, always within a broader strategy that includes diet, movement, sleep, stress management, and individual risk assessment.
The goal should not simply be to live longer, but to increase the years spent in good health, maintaining as much autonomy, metabolic function, physical capacity, and quality of life as possible.
Bibliographic References
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