on September 21, 2026
Chronological age and biological aging are not the same thing
Two people of the same age can have very different levels of functional capacity, body composition, metabolism, and vulnerability to chronic diseases. Chronological age is therefore only one part of the organism's biological story.
As we age, alterations can accumulate affecting the immune system, energy metabolism, muscle function, and vascular function. Among the most studied processes are low-grade chronic inflammation, cellular senescence, oxidative stress, and mitochondrial dysfunction.
These phenomena should not, however, be interpreted as independent processes. There is a complex network of interactions in which metabolic alterations, reduced physical activity, accumulation of adipose tissue, sleep disorders, and stress can contribute to maintaining a pro-inflammatory biological environment.
It is precisely this interaction that makes the concept of inflammaging interesting, i.e., the state of low-grade chronic systemic inflammation associated with aging.
Inflammaging: when inflammation becomes a chronic process
Inflammaging does not correspond to a single disease and does not necessarily identify an unrecognized infection.
Rather, it describes a condition characterized by greater persistent systemic inflammatory activity, in which immunosenescence, accumulation of senescent cells, alterations of tissue barriers, adiposity, metabolic changes, and reduced physical activity may contribute.
Over time, this inflammatory environment can be associated with greater vulnerability to sarcopenia, frailty, cardiovascular diseases, and metabolic disorders.
High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) are among the most studied biomarkers, but none of these parameters, taken individually, constitutes a diagnosis of inflammaging.
Its clinical significance emerges especially from the integration of biomarkers, clinical picture, and functional capacity.
Mitochondria: the energy center and an important sensor of cellular stress
Mitochondria play a fundamental role in energy production, but are also involved in the regulation of cellular stress and adaptive responses.
During cellular respiration, reactive oxygen species (ROS) are generated. Their production is not necessarily pathological. At physiological levels, ROS in fact participate in cellular signaling and can contribute to the activation of adaptive mechanisms, including those induced by exercise.
The problem arises when the production of reactive species exceeds the organism's ability to control them and repair the damage.
Excess ROS can damage lipids, proteins, and DNA, including mitochondrial DNA. At the same time, damaged mitochondria can release cellular components capable of activating innate immune responses.
This creates a possible circuit:
mitochondrial alteration → increased oxidative stress → pro-inflammatory signals → further mitochondrial alteration.
This circuit is particularly relevant in tissues with high energy demands, such as muscle, heart, and liver.
Oxidative stress: it does not simply mean "having too many free radicals"
The concept of oxidative stress is often simplified into the opposition between "free radicals" and "antioxidants".
From a biological point of view, the phenomenon is much more complex.
Reactive oxygen species also perform signaling functions. The organism possesses enzymatic and non-enzymatic systems capable of maintaining redox balance and adapting to environmental stimuli.
The physiological goal is therefore not to completely eliminate ROS, but to maintain a balance compatible with cellular function.
This concept is particularly important in the relationship between physical exercise and mitochondria. Physical activity generates a transient oxidative stimulus that can activate adaptive responses, including mechanisms of mitochondrial biogenesis and enhancement of endogenous defenses.
For this reason, the "more antioxidants = greater longevity" strategy does not represent a scientifically sustainable conclusion.
How to measure inflammaging
One of the problems of longevity medicine is distinguishing biologically interesting biomarkers from those that are truly useful in clinical practice.
hs-CRP can represent a practical indicator of low-grade systemic inflammation, but its significance increases when interpreted over time and within the clinical picture.
IL-6 and TNF-α are biomarkers more directly linked to immuno-inflammatory processes, but they show greater variability and lower clinical availability.
Albumin, complete blood count, ferritin, HbA1c, lipid profile, transaminases, and kidney function can also contribute to the overall assessment of biological status.
It is particularly important to integrate these parameters with functional indicators: grip strength, walking speed and quality, functional tests, body composition, and cardiorespiratory capacity.
A slightly elevated hs-CRP value in a physically robust person does not necessarily have the same meaning as a similar value in a person with loss of muscle mass, reduced strength, and slow recovery after stress.
Longevity medicine must therefore avoid turning a single biomarker into a diagnostic label.
Oxidative stress biomarkers
F2-isoprostanes and 8-OHdG represent some of the markers used to study lipid peroxidation and oxidative DNA damage, respectively.
They are interesting tools especially in the research field and in selected contexts, but their routine use still presents limitations related to biological and pre-analytical variability and the lack of universally shared decision intervals.
This leads to a practical consideration: for most people, it is not necessary to chase an increasing number of sophisticated biomarkers.
It is often more useful to identify and correct the modifiable drivers of inflammation and loss of metabolic efficiency.
Physical exercise as a biological intervention
Among the available interventions, physical activity represents one of the strategies with the most solid scientific basis.
Regular exercise acts simultaneously on mitochondrial function, insulin sensitivity, body composition, cardiorespiratory capacity, and muscle function.
An umbrella review published in 2025, which analyzed 13 systematic reviews on exercise in adults at least 60 years old, found that different exercise modalities can reduce CRP and TNF-α; for IL-6, the results are favorable but less uniform.
A meta-analysis of 40 studies including 49 trials and 1,898 older adults also found reductions in IL-6, TNF-α, and CRP with physical training, with effects varying according to the exercise modality and population characteristics.
These data reinforce a fundamental principle: healthy longevity cannot be separated from the ability to move.
Strength exercise takes on particular importance when the goal is to preserve muscle mass and functionality, while aerobic activity contributes significantly to cardiorespiratory capacity and cardiometabolic control.
Integrating the two components allows for simultaneous intervention on muscle reserve and cardiovascular reserve.
Nutrition: creating a favorable metabolic environment
Nutrition must also be interpreted not as a simple source of "antioxidants", but as one of the main determinants of the metabolic environment.
Dietary patterns rich in plant-based foods, fiber, legumes, whole grains, fruit, vegetables, nuts, and predominantly unsaturated fats, with the elimination of ultra-processed foods and excess energy, can contribute to a more favorable metabolic profile.
A meta-analysis from 2025 including 33 randomized trials and 3,476 participants observed a significant reduction in hs-CRP, IL-6, and IL-17 in the groups subjected to a Mediterranean diet compared to controls, while for TNF-α and other parameters, the results were not significant.
Another meta-analysis of clinical trials highlighted favorable effects of a Mediterranean diet enriched with olive oil on IL-6 and CRP/hs-CRP, while also highlighting high heterogeneity among the studies.
The central point is therefore not to "eat more antioxidants", but to build a dietary model capable of supporting metabolism, intestinal function, weight control, and micronutrient availability.
Sleep and obstructive apnea: often underestimated drivers
Sleep represents an essential component of metabolic and immune regulation.
Sleep fragmentation and obstructive sleep apnea (OSA) can lead to repeated episodes of intermittent hypoxia, increased sympathetic activity, oxidative stress, and inflammatory alterations.
A recent systematic review and meta-analysis found associations between OSA and several markers of biological aging, although the quality of the available studies varies.
Another meta-analysis found higher circulating concentrations of malondialdehyde, an indicator of lipid peroxidation, in patients with OSA compared to controls.
When significant snoring, reported breathing pauses, daytime sleepiness, or difficult-to-control hypertension are present, OSA screening can therefore represent a much more relevant intervention than simply adding a supplement.
OSA treatment can also change the inflammatory profile: a meta-analysis of studies on the use of CPAP found a reduction in IL-6 and other inflammatory markers, although the response may vary among patients.
Chronic stress and allostatic load
Chronic stress can interfere with sleep, physical activity, nutrition, and neuroendocrine regulation.
The relationship is bidirectional: persistent stress can worsen sleep quality, while sleep deprivation or fragmentation can increase vulnerability to stress.
For this reason, behavioral interventions such as stress management techniques, mindfulness, breathing training, and cognitive-behavioral interventions can be integrated into prevention programs.
Their primary goal should not necessarily be to "lower a cytokine", but to improve clinically relevant behaviors and functions: sleep quality, adherence to physical activity, stress management, and quality of life.
From the concept of "anti-aging" to longevity medicine
A program oriented toward longevity should start with the identification of the main modifiable drivers.
Visceral weight, sedentary lifestyle, and nutrition represent fundamental elements, but they are not the only ones. Respiratory sleep disorders, chronic pain, mood disorders, alcohol consumption, smoking, persistent infections, oral health, and medications that can influence metabolism and inflammation must also be considered.
Once the drivers are identified, the intervention should prioritize a foundation consisting of adequate nutrition, physical activity, regular sleep, and stress management.
Work on muscle mass takes on particular importance with age: preserving strength and functional capacity means increasing the reserve with which the organism faces diseases, immobilization, and other stresses.
Only then can the appropriateness of additional targeted interventions be evaluated, avoiding replacing fundamental strategies with a succession of supplementations.
Measuring to understand if the intervention works
A longevity program should be evaluated through measurable outcomes.
At approximately 12 weeks, they can be re-evaluated, according to the individual profile:
- hs-CRP trend;
- weight and waist circumference;
- HbA1c and lipid profile;
- blood pressure;
- grip strength;
- functional tests such as TUG and SPPB;
- exercise tolerance and aerobic capacity;
- body composition;
- sleep quality and daytime sleepiness.
The logic is fundamental: not to measure to accumulate data, but to measure to verify whether the intervention has produced a clinically useful change.
A biomarker that does not change, associated with an improvement in strength and functionality, should not necessarily be interpreted as a failure. Similarly, a reduction in an isolated inflammatory marker is not sufficient if the person continues to lose muscle mass and functional capacity.
Longevity as an adaptive capacity
Oxidative stress, mitochondrial dysfunction, and inflammaging are real biological processes, but they become truly useful in medicine when they are linked to modifiable conditions and clinical outcomes.
The most modern perspective on longevity, therefore, does not consist in trying to completely "turn off" inflammation or eliminate all ROS.
It consists in reducing pathological drivers while maintaining the body's ability to adapt to physiological stimuli.
Exercise represents a particularly clear example: it produces transient stress that can activate adaptive responses and, in the long term, improve mitochondrial and metabolic capacity. A very recent meta-analysis of 146 studies in older adults found overall improvements in numerous metabolic and inflammatory parameters with training, with differences between aerobic and resistance exercise.
The most clinically useful question, therefore, is not only:
"How can I reduce free radicals?"
The question becomes:
"Which modifiable levers can reduce the inflammatory load and improve energy and functional efficiency, preserving the body's normal adaptive signals?"
This is the shift from a generic anti-aging philosophy to a model of healthy longevity, in which the goal is not simply to live longer, but to maintain autonomy, strength, metabolic capacity, and biological resilience for longer.
Essential bibliographic references
- The effect of physical interventions in older adults on inflammatory markers (IL-6, IL-10, CRP, TNF-α): an umbrella review of systematic reviews and meta-analyses. Gerontology and Geriatric Medicine. 2025.
- Influence of different modes of exercise training on inflammatory markers in older adults with and without chronic diseases: A systematic review and meta-analysis. 2023.
- Exercise-induced inflammatory and metabolic adaptations in ageing: A meta-analytic compendium. 2026.
- Mediterranean Diet Reduces Inflammation in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials. 2025.
- The effects of the Mediterranean diet supplemented with olive oils on pro-inflammatory biomarkers and soluble adhesion molecules: a systematic review and meta-analysis of randomized controlled trials. 2025.
- Circulating markers of biological aging associated with obstructive sleep apnea or insomnia in adults: A systematic review and meta-analysis. Sleep Medicine Reviews. 2026.
- Effect of continuous positive airway pressure therapy on blood levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in obstructive sleep apnoea adults: A systematic review, meta-analysis and trial sequential analysis. 2024.
- Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. 2021;6.
- Association Between Beta-Carotene Supplementation and Mortality: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. 2022.
