November 24, 2020 - 3m 12s
Aging can be characterized by the progressive loss of physiological integrity, resulting in impaired functions and susceptibility for diseases and death. This biological deterioration is considered a major risk factor for cancer, cardiovascular diseases, diabetes and Alzheimer’s disease among others. At the cellular level, there are two key hallmarks of the aging process: shortening of telomere length and cellular senescence.
Telomeres are tandem nucleotide repeats located at the end of the chromosomes which maintain genomic stability. Telomeres shorten during replication (mitosis) due to the inherent inability to fully replicate the end part of the lagging DNA strand. Telomere length (TL), measuring between 4 to 15 kilobases, gradually shorten by ~20-40 bases per year and is associated with different diseases, low physical performance and cortical thinning of the brain. When TL reaches a critical length, cells cannot replicate and progress to senescence or programmed cell death. Goglin et al. demonstrated that adults with shorter TLs have increased mortality rates. Shortened TLs can be a direct inherited trait, but several environmental factors have also been associated with shortening TL including stress, lack of physical endurance activity, excess body mass index, smoking, chronic inflammation, vitamins deficiency and oxidative stress.
Cellular senescence is an arrest of the cell cycle which can be caused by telomere shortening, as well as other aging associated stimuli independent of TL such as non-telomeric DNA damage. The primary purpose of senescence is to prevent propagation of damaged cells by triggering their elimination via the immune system. The accumulation of senescent cells with aging reflects either an increase in the generation of these cells and/or a decrease in their clearance, which in turn aggravates the damage and contributes to aging.
A growing body of research has found several pharmacological agents that can reduce the telomere shortening rate. Several lifestyle interventions including endurance training, diets and supplements targeting cell metabolism and oxidative stress have reported relatively small effects (2-5%) on TL3.
Hyperbaric oxygen therapy (HBOT) utilizes 100% oxygen in an environmental pressure higher than one absolute atmospheres (ATA) to enhance the amount of oxygen dissolved in body’s tissues. Repeated intermittent hyperoxic exposures, using certain HBOT protocols, can induce physiological effects which normally occur during hypoxia in a hyperoxic environment, the so called hyperoxic-hypoxic paradox. In addition, it was recently demonstrated that HBOT can induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in cerebral blood flow. On the cellular level, it was demonstrated that HBOT can induce the expression of hypoxia induced factor (HIF), vascular endothelial growth factor (VEGF) and sirtuin (SIRT), stem cell proliferation, mitochondrial biogenesis, angiogenesis and neurogenesis. However, no study to date has examined HBOT’s effects on TL and senescent cell accumulation.
The aim of the current study was to evaluate whether HBOT affects TL and senescence-like T-cells population in aging adults.
Thirty-five individuals were assigned to HBOT. Five patients did not complete baseline assessments and were excluded. All 30 patients who completed baseline evaluations completed the interventions. Due to the low quality of blood samples (low number of cells or technician error), four patients were excluded from the telomere analysis and 10 patients from senescent cell análisis. There were no significant differences between the three groups.
For the first time, the current study aimed to evaluate the physiological effect on the cellular level in aging humans without any functional limiting disease. It was found that repeated daily HBOT sessions can increase PBMC telomere length by more than 20% in an aging population, with B cells having the most striking change. In addition, HBOT decreased the number of senescent cells by 10-37%, with T helper senescent cells being the most effected.
In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.
Hyperbaric oxygen therapy is a well-established treatment modality for non-healing wounds, radiation injuries as well as different hypoxic or ischemic events (such as carbon monoxide toxicity, infections, etc). In recent years, a growing evidence from pre-clinical as well as clinical trials demonstrate the efficacy of HBOT for neurological indications including idiopathic sudden sensorineural hearing loss, post stroke and post traumatic brain injury, central sensitization syndrome such as fibromyalgia síndrome and age related cognitive decline and animal models of Alzheimer’s disease.
Hachmo Y, Hadanny A, Abu Hamed R, Daniel-Kotovsky M, Catalogna M, Fishlev G, Lang E, Polak N, Doenyas K, Friedman M, Zemel Y, Bechor Y, Efrati S. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells : a prospective trial. Aging (Albany NY). 2020 Nov 18;12. doi: 10.18632/aging.202188. Epub ahead of print. PMID: 33206062.