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A summary of hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics

Hyperbaric oxygen therapy (HBOT) has emerged as a well-established treatment method for various medical conditions. Its noninvasive nature, safety profile, and wide clinical application make it a promising avenue for new indications, including aging and age-related diseases. Despite the belief that excessive oxygen might hasten aging, HBOT protocols within safe thresholds have shown considerable promise in combating aging.

Recent research has expanded our understanding of HBOT mechanisms, revealing significant overlaps with the targets of aging and age-related diseases. Preclinical and small-scale clinical studies have validated HBOT’s efficacy in combating aging from various angles. However, to fully utilize HBOT in aging therapies, a universally applicable protocol must be defined.

As aging significantly impacts quality of life and increases the risk of age-related diseases, effective interventions are crucial. Current strategies like stem cell therapy, young plasma transfusion, and lifestyle changes have shown promise but have limitations such as invasiveness and incomplete efficacy. In this context, HBOT stands out as a noninvasive, effective, and easily applicable approach to healthy aging. (See Figure 1).

HBOT, by delivering oxygen at increased pressures, triggers a range of physiological changes throughout the body. Its established mechanisms include promoting angiogenesis, alleviating inflammation, enhancing antioxidant defenses, and stimulating stem cells. The therapy’s advantages in aging intervention include its noninvasiveness, safety, and widespread clinical use.

This overview aims to elucidate how HBOT targets the aging process and its potential therapeutic implications, drawing from preclinical and clinical studies. By shedding light on HBOT’s role in healthy aging, we pave the way for further exploration and application in aging and geriatric research.

The Oxygen and Aging Paradox

The relationship between oxygen and aging presents a paradox: while oxygen is crucial for tissue health and overall survival, it also contributes to the aging process. Before we explore how Hyperbaric Oxygen Therapy (HBOT) can intervene in aging, let’s understand this delicate balance between oxygen’s protective and damaging effects in living organisms.

Oxygen generates reactive oxygen species (ROS), which, in controlled amounts, can be beneficial. However, excessive ROS production leads to oxidative damage to macromolecules like lipids, proteins, and DNA, accelerating aging. Interestingly, studies show that hypoxic conditions can mitigate aging markers in cell cultures, indicating a nuanced relationship between oxygen levels and aging. Both extremely high and low oxygen levels increase oxidative stress and decrease longevity, highlighting the complex nature of oxygen’s impact on aging. (See Figure 2).

HBOT triggers a biphasic response: while it initially increases ROS levels, repeated sessions prompt stronger antioxidant responses, reducing oxidative stress. Studies in healthy volunteers and middle-aged individuals show no significant increase in oxidative damage after multiple HBOT sessions, suggesting its safety. Importantly, HBOT’s fluctuating oxygen levels stimulate cellular protection without inducing harmful hypoxia effects.

This contradictory role of oxygen in aging can be understood through “Hormesis,” where sub-toxic doses of a harmful substance induced adaptations that protect against subsequent damage. Oxygen in HBOT may act similarly, with varying toxicity thresholds based on species, age, and tissue sensitivity. When administered within appropriate protocols, HBOT actively counteracts aging without exceeding toxicity thresholds, forming the foundation for its potential in aging interventions.

HBOT's Impact on Healthy Aging: Explained

In recent decades, significant strides have been made in understanding how aging works at the molecular level. This knowledge opens up numerous therapeutic avenues for addressing aging and age-related illnesses. Additionally, there is growing evidence supporting the benefits of Hyperbaric Oxygen Therapy (HBOT) in maintaining tissue health and promoting regeneration. Interestingly, HBOT targets many of the same mechanisms involved in aging and age-related diseases. A recent study revealed that HBOT can trigger significant changes in gene expression in healthy aging individuals, suggesting promising effects on aging at the molecular level. (See Figure 5).

Enhancement of Angiogenesis: Aging often leads to impaired blood vessel formation, which affects overall tissue health. HBOT has been shown to boost angiogenesis, the process of forming new blood vessels, by increasing the expression of key markers like HIF-1α. This effect is crucial for maintaining adequate blood supply to tissues, which is essential for their health and function.

Immunomodulation: Aging is associated with immune system dysregulation and chronic inflammation. HBOT appears to modulate immune responses, reducing inflammation by regulating various immune cell types like neutrophils and lymphocytes. This modulation helps in maintaining a balanced immune system, crucial for overall health.

Elevation of Antioxidant Activity: Oxidative stress, caused by an imbalance between free radicals and antioxidants, is a major contributor to aging. HBOT seems to enhance antioxidant defenses while also improving mitochondrial function, the powerhouse of cells. By doing so, it helps counteract oxidative stress, potentially slowing down the aging process. (See Figure 4).

Suppression of Cellular Senescence: Cellular senescence, where cells lose their ability to divide and function properly, is a hallmark of aging. HBOT has shown promise in reducing markers of cellular senescence, such as SA-β-gal activity and the expression of senescence-related proteins like p16 and p21. This suppression of cellular senescence may contribute to healthier aging.

Stem Cell Regulation: Stem cells play a crucial role in tissue regeneration and repair. With aging, there’s a decline in stem cell number and activity. HBOT appears to stimulate the mobilization and recruitment of stem cells from bone marrow. It also promotes stem cell proliferation, differentiation, and secretion of beneficial proteins, which are essential for tissue regeneration.

HBOTs Implicit Therapeutic Aging Intervention

HBOT holds promise as a therapeutic intervention for various aspects of aging, including cognitive decline, skin aging, metabolic disorders, musculoskeletal health, and cardiopulmonary function. Further research is necessary to understand its mechanisms and optimize treatment protocols for maximum benefit in aging populations.

Cognitive Improvement: HBOT has shown promising results in enhancing cognitive function, particularly in healthy adults and aging populations. Studies indicate improvements in memory, attention, and executive functions, suggesting potential benefits for both normal aging and neurodegenerative conditions like Alzheimer’s disease.

Skin Rejuvenation: HBOT exhibits rejuvenating effects on skin, addressing both intrinsic aging and photoaging caused by UV radiation. It stimulates collagen production, reduces senescent cells, and enhances skin elasticity, offering potential as a treatment for various skin conditions and aging-related changes.

Metabolism Regulation: HBOT shows potential in regulating glucose metabolism, improving insulin sensitivity, and reducing markers of inflammation associated with age-related metabolic disorders like diabetes and metabolic syndrome. Animal studies and clinical trials indicate promising results, suggesting HBOT as a potential intervention for metabolic health in aging populations.

Musculoskeletal Restoration: HBOT demonstrates effectiveness in preventing muscle and bone loss associated with aging, particularly in conditions like sarcopenia and osteoporosis. Animal studies suggest that HBOT may help maintain muscle mass, prevent bone loss, and improve bone structure and strength in aging individuals.

Cardiopulmonary Function Improvement: HBOT shows positive effects on aging-related decline in cardiopulmonary function. It improves myocardial function and diastolic parameters in aging hearts, while also modestly enhancing pulmonary function in elderly individuals without chronic lung diseases.

Limitations and Future Directions

In conclusion, this review emphasizes the extensive advantages of HBOT in promoting healthy aging. Nonetheless, the various HBOT protocols and methodologies complicate the comparison and integration of research findings. The development of universally applicable HBOT protocols suited to the aging population beyond current therapeutic uses is urgently needed inorder to compile more accurate data.

Recent advancements in HBOT research have introduced innovative protocols which hold promise in eliciting positive changes linked to aging. Despite encouraging results from preclinical studies, concerns regarding the potential adverse effects of HBOT continue, emphasizing the necessity of weighing benefits against risks, particularly among older individuals. Looking ahead, refining HBOT protocols and addressing safety considerations are pivotal for its effective clinical deployment in promoting healthy aging. While existing insights offer valuable groundwork, further investigation is essential to fine-tune protocols and uncover fresh revelations in leveraging HBOT’s potential against age-related ailments.

Please note that this is a simplified summary based on the original content of Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics, an open access article found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156818/. It is not a derivative, adaptation or remix of the source material available on PubMed Central; rather, it serves as a condensed, simplified version. For the complete publication, please visit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156818/.