Hyperbaric Oxygen Therapy and Longevity: Targeting the Cellular Hallmarks of Ageing

Advanced HBOT chamber featuring integrated monitoring systems and automated controls for precise therapeutic oxygen treatment delivery

The quest to understand and reverse biological ageing has gained considerable momentum, with researchers identifying twelve distinct hallmarks that characterise the ageing process at the cellular level¹.

Among emerging therapeutic interventions, hyperbaric oxygen therapy (HBOT) has demonstrated measurable effects on biological age biomarkers, offering a potential pathway to cellular rejuvenation.

The Israeli Breakthrough: Telomeres and Cellular Senescence

A landmark prospective study at Shamir Medical Center in Israel has provided compelling evidence for HBOT's anti-ageing effects². Researchers examined 30 healthy adults (mean age 68.4 years) who underwent 60 daily HBOT sessions over three months. The results were remarkable. Telomere length in immune cells increased by over 20%, with B cells showing a 37.6% increase following treatment.

Equally significant was the therapy's impact on cellular senescence. The study demonstrated substantial reductions in senescent immune cells, with senescent T helper cells decreasing by 37.3% and senescent T cytotoxic cells by 11.0%. These findings represent the first human evidence that a therapeutic intervention can meaningfully reverse two fundamental hallmarks of ageing.

Targeting Three Key Hallmarks of Ageing

HBOT appears to target multiple hallmarks from the twelve identified by López-Otín and colleagues¹:

1. Telomere Attrition

Telomeres serve as protective caps on chromosomes, shortening with each cell division until cells enter senescence. The Israeli study's demonstration of significant telomere lengthening suggests HBOT may reset this cellular ageing clock.

The mechanism likely involves enhanced antioxidant defences, as oxidative stress is a primary driver of telomere shortening³.

2. Cellular Senescence

Senescent cells accumulate with age and contribute to tissue dysfunction through inflammatory secretions. HBOT's proven ability to reduce senescent cell populations represents a direct intervention against this hallmark.

A subsequent skin study confirmed these findings, showing significant decreases in senescent cells alongside improvements in collagen density and elastic fibre structure⁴.

3. Mitochondrial Dysfunction

Recent research has revealed HBOT's profound effects on mitochondrial function. A 2024 study in cardiomyocytes demonstrated that HBOT increased mitochondrial biogenesis markers and enhanced respiratory function, with basal respiration increasing 2.1-fold and ATP production rising 2.2-fold⁵.

This mitochondrial rejuvenation directly addresses the declining cellular energetics that characterise ageing.

The Hyperoxic-Hypoxic Paradox

The mechanism underlying HBOT's benefits appears paradoxical. Whilst high oxygen concentrations might be expected to increase oxidative stress, intermittent hyperoxic exposure triggers protective responses.

This "hyperoxic-hypoxic paradox" involves upregulation of hypoxia-inducible factor (HIF-1α) and antioxidant genes, creating enhanced cellular resilience⁶. The treatment provides controlled oxidative stress that stimulates hormetic responses, beneficial stressors that strengthen rather than damage cells.

Measurable Biomarker Improvements

Beyond cellular mechanisms, HBOT produces measurable improvements in biological age biomarkers. The Israeli team's skin ageing study demonstrated increases in collagen density, elastic fibre length, and blood vessel formation, the objective measures of tissue rejuvenation⁴.

These structural improvements were accompanied by functional enhancements, including better tissue elasticity and reduced fibre fragmentation.

Systematic reviews have documented HBOT's effects across multiple biological systems, including enhanced cognitive function, increased stem cell mobilisation, and upregulated expression of genes associated with cellular repair and regeneration³.

These broad-spectrum effects suggest HBOT influences fundamental ageing processes rather than targeting isolated pathways.

A Critical Perspective

Whilst the evidence for HBOT's anti-ageing effects is compelling, several areas warrant further investigation to optimise clinical protocols. Current human studies have relatively small sample sizes; the pivotal Israeli telomere study included only 25 participants in the final telomere analysis.

Long-term durability of observed effects remains unknown, with follow-up periods typically lasting weeks rather than years.

The optimal treatment protocol has yet to be established. The Israeli studies employed 60 sessions over three months, but ongoing research continues to refine optimal treatment parameters for maximum benefit. Individual responses may vary significantly, and potential side effects including barotrauma and visual changes require careful monitoring⁶.

Clinical Implications and Future Directions

The current evidence suggests HBOT represents a legitimate intervention targeting multiple hallmarks of ageing simultaneously. Unlike many proposed anti-ageing therapies, HBOT's effects are measurable through established biomarkers and demonstrate consistency across different tissue types.

For clinicians in longevity medicine, these findings offer an evidence-based intervention that may complement other healthspan-extending strategies. However, the field requires larger, longer-term studies to establish optimal protocols and confirm durability of benefits.

Economic and practical considerations also merit attention, as HBOT requires specialised equipment and trained personnel.

Final Thoughts on Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy represents a paradigm shift in ageing intervention. By demonstrating measurable effects on telomere length, cellular senescence, and mitochondrial function, HBOT offers a scientifically grounded method for targeting fundamental mechanisms of cellular ageing.

The Israeli studies have opened a new chapter in longevity medicine, suggesting cellular ageing may be more malleable than previously thought.

Whilst questions remain about optimal implementation and long-term effects, current evidence provides compelling justification for continued research and careful clinical application. As our understanding advances, HBOT may well become a cornerstone therapy in the pursuit of healthy human longevity.

References

1.            López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: An expanding universe. Cell 186, 243-278 (2023).

2.            Hachmo, Y. et al. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging 12, 22445-22456 (2020).

3.            Tessema, B. et al. Effects of hyperoxia on aging biomarkers: a systematic review. Front. Aging 3, 783144 (2022).

4.            Hachmo, Y. et al. The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial. Aging 13, 24500-24510 (2021).

5.            Young, H. Y. et al. Hyperbaric oxygen increases mitochondrial biogenesis and function with oxidative stress in HL-1 cardiomyocytes. J. Appl. Physiol. 138, 247-258 (2025).

Gupta, M. & Rathored, J. Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging. Front. Aging 5, 1368982 (2024).