Over the past decade, scientists have identified key biological “hallmarks of ageing”, the core processes that drive decline in health over time.
First outlined in Cell (López-Otín et al., 2013) and expanded in 2023, these twelve hallmarks form the blueprint for understanding why we age and where targeted interventions may extend both healthspan and lifespan.
Functional medicine offers practical, evidence-based ways to address each hallmark by focusing on personalised nutrition, lifestyle, and advanced testing strategies. Here’s how the hallmarks connect to longevity, and some actionable steps to support them.
1. Genomic Instability
What it means: Accumulation of DNA damage from environmental toxins, poor repair, or oxidative stress.
- Support detoxification: Sulforaphane, glutathione precursors.
- Increase antioxidants: Berries, green tea, vitamin C/E.
- Reduce exposures: Smoking, pesticides, heavy metals.
2. Telomere Attrition
What it means: Shortening of chromosome ends, limiting cell renewal.
- Stress management and meditation: Shown to preserve telomere length.
- Omega-3 fatty acids and vitamin D support.
- Regular exercise: Especially endurance and strength training.
3. Epigenetic Alterations
What it means: “Switching off” or “on” genes in ways that promote ageing.
- Methylation support: B vitamins (B12, folate, B6).
- Plant-rich diets: Polyphenols (curcumin, resveratrol, green tea).
- Intermittent fasting and caloric restriction patterns.
4. Loss of Proteostasis
What it means: Failure to maintain properly folded proteins: misfolding, aggregation, neurodegeneration.
- Support autophagy: Fasting and exercise.
- Adequate protein intake: For repair.
- Polyphenols: Quercetin, spermidine to promote cellular cleaning.
5. Deregulated Nutrient Sensing
What it means: Ageing of metabolic pathways like insulin/IGF-1, mTOR, AMPK, and sirtuins.
- Balanced glucose control: Low-glycaemic diet, fibre.
- Time-restricted eating: To activate AMPK.
- Nutraceuticals under study: Berberine, resveratrol, NAD+ boosters.
6. Mitochondrial Dysfunction
What it means: Decline in energy production, rise in free radicals.
- Exercise: The strongest mitochondrial stimulator.
- Nutrients: CoQ10, L-carnitine, alpha-lipoic acid.
- Cold exposure and sauna: To induce mitochondrial resilience.
7. Cellular Senescence
What it means: Old, non-dividing cells that secrete inflammatory molecules.
- Senolytic compounds studied: Quercetin, fisetin.
- Exercise and fasting: To reduce senescent load.
- Monitor inflammation markers: Through functional testing.
8. Stem Cell Exhaustion
What it means: Reduced regenerative capacity in tissues.
- Sleep optimisation: Deep sleep promotes stem cell renewal.
- Protein and micronutrient sufficiency: Iron, zinc.
- Avoid chronic toxin exposure: Alcohol, smoking.
9. Altered Intercellular Communication
What it means: Ageing cells send “pro-inflammatory signals” that damage tissues.
- Anti-inflammatory nutrition: Mediterranean-style diet, omega-3s.
- Stress reduction: To balance cortisol and immune signals.
- Gut health optimisation: To reduce systemic inflammation.
10. Dysbiosis (Microbiome Imbalance)
What it means: Loss of microbial diversity, results in impaired immunity, inflammation, gut–brain axis changes.
- Fibre-rich diet: With 30+ plant foods weekly.
- Targeted probiotics and prebiotics.
- Advanced stool analysis: To guide personalised strategies.
11. Compromised Autophagy
What it means: Impaired cellular “recycling system” that clears damaged components.
- Intermittent fasting and caloric restriction.
- Exercise: Stimulates autophagy pathways.
- Nutrients: Spermidine and trehalose under investigation.
12. Splicing Dysregulation
What it means: Age-related errors in RNA splicing that disrupt protein production.
- Polyphenol-rich diets: Flavonoids shown to influence splicing machinery.
- Support mitochondrial and epigenetic health: As indirect regulators.
- Adequate sleep: To optimise circadian regulation of gene expression.
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Key Takeaway
The hallmarks of ageing reveal where biology goes wrong as we grow older. Functional medicine provides a framework for acting on these hallmarks, not just treating disease after it arises, but targeting root causes that drive longevity. By combining advanced testing with personalised interventions in nutrition, lifestyle, and supplementation, it is possible to influence the trajectory of ageing itself. Shifting from decline to resilience.
References
- López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217.
- López-Otín, C., Kroemer, G., Partridge, L., Serrano, M., & Blasco, M. A. (2023). Hallmarks of aging: An expanding universe. Cell, 186(2), 243–278.
- Blackburn, E. H., Epel, E. S., & Lin, J. (2015). Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science, 350(6265), 1193–1198.
- Singh, C. K., Chhabra, G., Ndiaye, M. A., & Ahmad, N. (2020). Functional relevance of sirtuins in aging and age-related diseases. Aging Cell, 19(4), e13120.
- Kennedy, B. K., et al. (2014). Geroscience: Linking aging to chronic disease. Cell, 159(4), 709–713.
- Zhang, Y., & Jiang, W. (2015). Polyphenols in the prevention and treatment of neurodegenerative diseases. Molecular Neurobiology, 51(2), 545–560.
- Valenzano, D. R., et al. (2017). Nutrient sensing pathways regulating aging and life span. Cold Spring Harbor Perspectives in Biology, 9(3), a025148.
- O’Toole, P. W., & Jeffery, I. B. (2015). Gut microbiota and aging. Science, 350(6265), 1214–1215.
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