Introduction — Ageing isn’t an age; it’s a biological trajectory

For decades, ageing was approached as a mechanical consequence of time: the mere accumulation of years leading to a progressive, inevitable decline in biological function. This chronological reading, inherited from descriptive twentieth-century medicine, profoundly shaped medical, nutritional and preventive frameworks.

Contemporary advances in cellular biology, epigenetics and systems biology have fundamentally challenged that paradigm. Ageing is now understood as an active biological process, driven by a progressive drift in the living system’s functional organisation. This drift long precedes the onset of chronic disease and explains why two individuals of the same chronological age can display radically different health states [1,2].

Within this framework, biological ageing can be defined as the progressive loss of coherence, plasticity and adaptive capacity across biological networks. This loss is expressed at the cellular level — mitochondria, metabolic signalling, inflammation, epigenetics — but also at the level of tissues and physiological systems [3–6].

The scientifically relevant question is therefore no longer whether we can “defeat” ageing — which biology does not allow — but to what extent we can shape its trajectory, slow its harmful mechanisms, and preserve functional quality over time.

I — Biological ageing: what we measure (and what we don’t)

One of the major turning points in ageing research has been the development of tools capable of objectifying biological age. Epigenetic clocks, based on DNA methylation profiles, have shown that certain biological signatures are robustly associated with morbidity, frailty and mortality, independently of chronological age [7–9].

However, interpreting these tools requires strict scientific discipline. Recent work has highlighted that these clocks aggregate several types of biological signals:

• markers of cumulative damage, linked to chronic inflammation, oxidative stress and metabolic dysfunction;
• but also markers of adaptive responses, reflecting the living system’s plasticity under environmental constraints (energy restriction, physical activity, acute stress) [10].

This distinction is crucial. A change in a biological-age marker does not necessarily reflect irreversible deterioration. Biological ageing is neither a fixed state nor a strictly linear process: it is a dynamic trajectory resulting from the balance between stress, repair and adaptation.

Understanding this nuance helps avoid two major pitfalls:
– the unrealistic promise of “rejuvenation”,
– and biological fatalism, which assumes ageing is always passively endured.

II — Ageing as the progressive disorganisation of biological networks

Major contemporary syntheses — notably those published in Cell — have profoundly reshaped our understanding of ageing. It is no longer described as the consequence of a single mechanism, but as the progressive convergence of interconnected, systemic imbalances [1,2].

These imbalances notably involve:

• mitochondrial dysfunction and loss of bioenergetic capacity,
• dysregulation of nutrient-sensing pathways (mTOR, AMPK, IGF-1, sirtuins),
• chronic low-grade inflammation (inflammaging),
• persistent oxidative and nitrosative stress,
• environment-driven epigenetic alterations,
• accumulation of senescent cells,
• loss of immune and metabolic plasticity [11–15].

These mechanisms never operate in isolation. They reinforce one another through feedback loops. Inefficient mitochondria generate more oxidative stress; oxidative stress fuels inflammation; inflammation disrupts metabolic signalling; metabolic dysregulation amplifies epigenetic alterations.

Biological ageing therefore corresponds to a progressive desynchronisation of regulatory systems — far more than a simple accumulation of “damage”.

III — Chronic inflammation: a central driver of functional ageing

Among these mechanisms, chronic low-grade inflammation occupies a central position. Work published in The Lancet has shown that persistent inflammation is a cross-cutting driver linking nutrition, metabolism, immunity and ageing [3,4].

Unlike acute inflammation, which is protective, chronic inflammation is silent, diffuse and self-sustaining. It often results from prolonged exposure to:

• a pro-inflammatory diet,
• chronic energy overload,
• gut dysbiosis,
• persistent metabolic and oxidative stress.

At the cellular level, this inflammation activates pathways such as NF-κB and the NLRP3 inflammasome, which interfere with cellular repair, renewal and differentiation mechanisms [16–18].

Clinically, inflammaging is closely associated with frailty, loss of muscle mass, metabolic disorders, and cardiovascular and neurodegenerative disease. Slowing biological ageing therefore implies, first and foremost, durably reducing this inflammatory burden.

IV — Mitochondria: the energy engine at the heart of longevity

Mitochondria play a pivotal role in ageing biology. They do not merely produce energy: they regulate oxidative stress, apoptosis, innate immunity, metabolic signalling and gene expression [19].

With age, mitochondria progressively lose efficiency. This decline leads to:

• reduced ATP production,
• increased ROS generation,
• impaired quality control (mitophagy),
• activation of inflammatory pathways.

Evidence from Molecular Cell and Nature indicates that mitochondrial dysfunction often precedes the clinical onset of age-related diseases [19–21].

Preserving mitochondrial function is therefore not a secondary objective, but an upstream lever of functional ageing.

V — Nutrition and nutrient sensing: when nutrition becomes biological information

Modern nutrition science goes far beyond caloric intake. Nutrients are perceived by cells as biological signals, interpreted through highly conserved regulatory pathways: mTOR, AMPK, IGF-1 and sirtuins [22–25].

These pathways continuously determine the cell’s biological priorities:

• growth or maintenance,
• storage or oxidation,
• repair or adaptive stress.

Chronic exposure to incoherent nutritional signals (excess rapid sugars, oxidised lipids, micronutrient insufficiencies) disrupts these pathways and promotes accelerated biological ageing.

Conversely, a coherent nutritional environment supports cellular maintenance, autophagy, metabolic resilience and epigenetic stability.

VI — From micronutrition to Cellular Nutrition: changing scale

Clinical micronutrition represented a major advance by identifying cells’ functional needs: vitamins, minerals, trace elements, polyphenols and essential fatty acids [26–28].

However, given the complexity of the biological networks involved in ageing, correcting isolated deficiencies shows its limits. This is where Cellular Nutrition emerges as a logical evolution.

Cellular Nutrition aims to restore the coherence of the cellular environment by acting simultaneously on:

• mitochondrial energy,
• chronic inflammation,
• redox balance,
• the gut microbiota,
• the quality of nutritional signals perceived by the cell [29–33].

It is not based on accumulating actives, but on their functional articulation, aligned with systems biology.

VII — Human evidence: slowing the trajectory, not reversing time

Human clinical trials confirm that certain nutritional and lifestyle interventions can influence markers of biological ageing — but with effects that are modest, progressive and context-dependent.

The CALERIE and DO-HEALTH studies show that coherent interventions can slow the pace of biological ageing, without producing dramatic “rejuvenation” [14,15].

These results are essential: they demonstrate that biological prevention is possible, but it unfolds over the long term — far from quick-fix promises.

VIII — Cellular senescence: regulate rather than eradicate

Cellular senescence is a protective physiological mechanism that becomes harmful when it accumulates chronically. Senescent cells secrete pro-inflammatory mediators (the SASP) that degrade the tissue environment [17,18].

Nutritional approaches aim to reduce the conditions that promote chronic senescence, rather than abruptly eliminating these cells — which could carry detrimental consequences.

IX — Blue Zones: population-level validation of biological coherence

Blue Zones illustrate, at a population scale, principles described in the laboratory. These populations share durable environmental coherence: minimally processed diets, high micronutrient density, moderate physical activity, and low inflammatory burden [22–25].

They show that functional longevity emerges from coherence over time, not from the extreme optimisation of a single isolated parameter.

Conclusion — Slowing biological ageing: a strategy of coherence and long-term consistency

Biological ageing is neither fully programmable nor entirely endured. It results from the continuous interaction between cells and their informational environment.

By seeking to optimise the coherence of biological signals perceived by the cell, Cellular Nutrition represents one of the most credible levers available today to slow the drift of biological networks, preserve function, and support healthy ageing.

It does not promise the impossible. It aligns with the biological, clinical and scientific reality of living systems.

Bibliography

1. Conceptual frameworks of biological ageing

[1] López-Otín, C. et al. (2013)
The hallmarks of aging
Cell, 153(6), 1194–1217.
Available at: https://www.cell.com/cell/fulltext/S0092-8674(13)00645-4

What the paper demonstrates
This foundational publication proposes a mechanistic structure of ageing through nine “hallmarks”, derived from converging genetic, cellular and pathophysiological evidence. It shows that ageing cannot be reduced to a passive process, but reflects a progressive drift in maintenance mechanisms.

Type of evidence
Integrative conceptual review (Cell), grounded in decades of experimental animal and human data.

Limitations
The hallmarks are neither independent nor absolutely hierarchical. Their relative weight varies across tissues and contexts.

Relevance to this article
A doctrinal cornerstone: slowing ageing requires acting on multiple mechanisms simultaneously, not on a single factor.

[2] López-Otín, C. et al. (2023)
Hallmarks of aging: An expanding universe
Cell, 186(2), 243–278.
Available at: https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0

What the paper demonstrates
This update expands the hallmarks to 12 mechanisms, explicitly integrating chronic inflammation, dysbiosis and impaired autophagy. It strengthens a systems-biology reading of ageing.

Type of evidence
High-level critical review integrating multi-omics, computational biology and human data.

Limitations
Still a conceptual framework rather than a strict causal model.

Relevance
Scientifically legitimises placing microbiota–inflammation–metabolism at the heart of ageing prevention.

2. Epigenetics and biological plasticity

[3] Jaenisch, R. and Bird, A. (2003)
Epigenetic regulation of gene expression
Nature Genetics, 33(Suppl), 245–254.
Available at: https://www.nature.com/articles/ng1089

What the paper demonstrates
Establishes that gene expression is contextual, dependent on environmental signals integrated by the cell through epigenetic mechanisms.

Type of evidence
Foundational molecular-biology review.

Limitations
Does not address ageing directly, but provides mechanistic foundations.

Relevance
Theoretical basis for nutrition as biological information.

[4] Feil, R. and Fraga, M.F. (2012)
Epigenetics and the environment
Nature Reviews Genetics, 13, 97–109.
Available at: https://www.nature.com/articles/nrg3142

What the paper demonstrates
Shows that nutrition, inflammation, stress and environmental exposures can durably modify the human epigenome.

Type of evidence
Integrative review spanning human and animal evidence.

Limitations
Substantial inter-individual heterogeneity.

Relevance
Supports progressive, cumulative prevention — not one-off interventions.

3. Chronic inflammation and functional ageing

[5] Gregor, M.F. and Hotamisligil, G.S. (2011)
Inflammatory mechanisms in obesity
The Lancet, 378, 253–262.
Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60827-5/fulltext

What the paper demonstrates
Describes meta-inflammation as a mechanism linking nutritional excess, metabolic dysregulation and chronic inflammation.

Type of evidence
Mechanistic and clinical review.

Limitations
Primary focus on obesity; extrapolation to ageing requires care.

Relevance
A strong causal bridge: nutrition → inflammation → ageing.

[6] Ferrucci, L. and Fabbri, E. (2018)
Inflammageing
The Lancet Diabetes & Endocrinology, 6, 505–514.
Available at: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30104-2/fulltext

What the paper demonstrates
Shows chronic inflammation predicts frailty, loss of autonomy and mortality.

Type of evidence
Clinical longitudinal synthesis.

Limitations
Strong correlation, but multifactorial causality.

Relevance
Slowing ageing means delaying frailty.

[7] Franceschi, C. et al. (2018)
Inflammaging and longevity
Nature Reviews Endocrinology, 14, 576–590.
Available at: https://www.nature.com/articles/s41574-018-0059-4

What the paper demonstrates
A systems reading of inflammaging as an adaptive imbalance.

Type of evidence
Systems-biology review.

Limitations
No direct intervention tested.

Relevance
Justifies a coherent multi-lever approach.

4. Biological age and clocks

[8] Horvath, S. (2013)
DNA methylation age
Genome Biology, 14, R115.
Available at: https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-10-r115

What the paper demonstrates
Creates the first multi-tissue epigenetic clock.

Type of evidence
Computational DNAm analysis.

Limitations
Descriptive measure, not causal.

Relevance
Enables discussion of measurable biological age.

[9] Levine, M.E. et al. (2018)
PhenoAge
Aging, 10, 573–591.
Available at: https://www.aging-us.com/article/101414/text

What the paper demonstrates
Links DNAm-based age to clinical health parameters.

Type of evidence
Longitudinal cohorts.

Limitations
Influenced by inflammation and cell-type composition.

Relevance
Connects biology to clinical outcomes.

[10] Ying, K. et al. (2024)
Damage vs Adaptation epigenetic age
Nature Aging.
Available at: https://www.nature.com/articles/s43587-024-00645-9

What the paper demonstrates
Introduces a conceptual separation between deleterious and adaptive epigenetic ageing signatures.

Type of evidence
Integrated causal approaches.

Limitations
Still early for routine clinical use.

Relevance
A key scientific safeguard against “rejuvenation” claims.

5. Mitochondria and bioenergetics

[11] Sun, N., Youle, R.J. and Finkel, T. (2016)
The mitochondrial basis of aging
Molecular Cell, 61, 654–666.
Available at: https://pubmed.ncbi.nlm.nih.gov/26942670/

What the paper demonstrates
Mitochondrial ageing is an upstream driver, not merely a downstream consequence.

Type of evidence
Mechanistic review.

Limitations
Animal models predominate.

Relevance
Justifies mitochondrial centrality.

6. Human interventions

[12] Waziry, R. et al. (2023)
CALERIE trial
Nature Aging.
Available at: https://www.nature.com/articles/s43587-022-00357-y

What the paper demonstrates
Caloric restriction slows the pace of biological ageing.

Type of evidence
Randomised human trial.

Limitations
Modest effects; adherence varies.

Relevance
Human proof that trajectories are modifiable.

[13] Bischoff-Ferrari, H.A. et al. (2025)
DO-HEALTH
Nature Aging.
Available at: https://www.nature.com/articles/s43587-024-00793-y

What the paper demonstrates
Modest additive effects of nutrition plus exercise.

Type of evidence
Multicentre RCT.

Limitations
Clocks are proxies.

Relevance
Supports combined strategies.

7. Cellular senescence

[14] Campisi, J. and d’Adda di Fagagna, F. (2007)
Cellular senescence
Nature Reviews Molecular Cell Biology.
Available at: https://www.nature.com/articles/nrm2233

What the paper demonstrates
Senescence is protective initially, then becomes harmful when it accumulates.

Type of evidence
Mechanistic review.

Relevance
Supports upstream regulation strategies.

8. Environment and population longevity

[15] Argentieri, M.A. et al. (2025)
Environmental vs genetic aging
Nature Medicine.
Available at: https://www.nature.com/articles/s41591-024-03483-9

What the paper demonstrates
The exposome weighs more heavily than genetics on mortality.

Type of evidence
Very large cohorts (UK Biobank).

Limitations
Potential confounding.

Relevance
A scientific foundation for prevention.

Post Scriptum

Taken together, these studies converge on a clear conclusion: biological ageing is partially modifiable — not through spectacular interventions, but through coherent, durable optimisation of the cellular environment.

That is precisely the scientific space occupied by Cellular Nutrition.