Mitochondrial dysfunction is a hallmark of metabolic decline during aging. Chini and colleagues found that cells consume less oxygen, have increased lactate levels, and possess irregular mitochondria (Camacho-Pereira et al., 2016). (CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Camacho-Pereira J, Tarragó MG, Chini CCS, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN Cell Metab. 2016 Jun 14; 23(6):1127-1139.

• (1) the gene expression of PGC-1α, silent mating type information regulation 2 homologs 1 (SIRT1) and VEGF, and increased the number of mitochondria, as proven by real-time PCR and immunohistochemistry,
• (2) muscle fiber switching in the TA muscle, as proven by isolation of myosin heavy chain and ATPase staining.

• Injured muscle fibres were completely repaired at week six in the CO2-treated group but only partially repaired in the untreated group.
• expression levels of genes and proteins related to muscle protein synthesis were significantly higher in the CO2-treated group 
• significantly more capillaries four weeks after injury.

• CO2 therapy improved limited-extension ROM in the prevention group at 2 weeks (22° ± 2°) and 4 weeks (29° ± 1°) and in the treatment group at 2 weeks
• Muscular factors decreased in treated rats in the prevention group at 2 weeks (8° ± 2°) and 4 weeks (14°± 1°) and in the treatment group at 2 weeks (14 ± 1°) compared with untreated rats (15° ± 1°, 4.85-9.42; 16° ± 1°, 1.24-3.86; and 17° ± 2°, 1.16-5.34, respectively; all p < 0.05).

• We reported that carbon dioxide (CO2) water bathing accelerates skeletal muscle regeneration
• MyoD and myogenin play roles in muscle regeneration
• Tap water and CO2 (1,000 ppm) water bathing were performed at 37 °C for 30 minutes once a day.

• Laser Doppler perfusion imaging demonstrated that the blood flow in the fractured limb was significantly greater at weeks 2 and 3 in the CO2/hydrogel group
• (p < 0.05; 95% CI for the difference, 8.4% to 22.4% and 6.7% to 19.0%, respectively).
• Gene expression of chondrogenic, osteogenic, and angiogenic markers was significantly greater in the CO2/hydrogel group at several time points.

• Radiographically, bone healing rate was significantly higher in the CO2 group than in the control group at 4 weeks (18.2% vs. 72.7%).
• The ultimate stress, extrinsic stiffness, and failure energy were significantly greater in the CO2 group than in the control group at 4 weeks
• Gene expression of vascular endothelial growth factor in the CO2 group was significantly greater than that in the control group at 3 weeks

• The fracture union rate was significantly higher in the 3w-CO2 group than in the control group (p < 0.05). Histological assessment revealed promotion of endochondral ossification in the 3w-CO2 group than in the control group. In the biomechanical assessment, all evaluation items related to bone strength were significantly higher in the 3w-CO2 group than in the control group
• CONCLUSIONS: The present study, conducted using an animal model, demonstrated that continuous carbon dioxide application throughout the process of fracture repair was effective in enhancing fracture healing.

• RESULTS: Nineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2 therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner.
• CONCLUSIONS: The findings of the present study revealed that CO2 therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs.

• Muscle weight was significantly higher in the CO2 group than in the control group.
• Histological analysis revealed that the muscle fiber cross-sectional area was reduced in both groups. Nevertheless, the extent of atrophy was lesser in the CO2 group.
• Muscle fibers in the control group tended to change into fast muscle fibers. Vascular staining revealed that more capillary vessels surrounded the muscle fibers in the CO2 group

• The acceleration of nerve regeneration remains a clinical challenge.
• Scores for the sciatic function index and pinprick test were significantly higher in the CO2 group than control group.
• The muscle wet weight ratios of the tibialis anterior and soleus muscles were higher in the CO2 group than control group.
• Electrophysiological examination showed that the CO2 group had higher compound motor action potential amplitudes and shorter distal motor latency than the control group.

• Exogenous CO2 by transcutaneous delivery promotes muscle fibre-type switching to increase endurance power in skeletal muscles.
• Running performance improved over the treatment period in the CO2 group, with a concomitant switch in muscle fibres to slow-type.
• The mitochondrial DNA content and capillary density in the CO2 group increased.
• CO2 was beneficial for performance and muscle development during endurance exercise

• Hyperglycemia impairs oxidative capacity in skeletal muscle.
• Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle.
• These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.

• Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression.
• In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation.
• Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells in vitro

• Hypoxia plays a significant role in cancer progression, including metastatic bone tumors.
• We previously reported that transcutaneous carbon dioxide (CO2) application could decrease tumor progression through the improvement of intratumor hypoxia.
• In vivo results by μCT revealed that bone destruction was suppressed by transcutaneous CO2

• Despite substantial improvements in surgery and chemotherapy, metastasis remains a major cause of fatal outcomes
• increases expressions of hypoxia inducible factor (HIF)-1α, matrix metalloproteinase (MMP)-2 and MMP-9, and can induce invasiveness
• As we previously showed a novel transcutaneous CO2 application to decrease HIF-1α expression and induce apoptosis in malignant fibrous histiocytoma, we hypothesize that transcutaneous CO2 application could suppress metastatic potential of osteosarcoma by improving hypoxic conditions.

• present study, we investigated the relationship between the duration, frequency, and treatment interval of transcutaneous CO2 application and antitumor effects in murine xenograft models
• Murine xenograft models of three types of human tumors (breast cancer, osteosarcoma, and malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma)
• apoptosis was significantly induced by CO2 treatment for ≥10 min, and a significant decrease in tumor volume was observed with CO2 treatments of >5 min.

• However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs.
• In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts.
• Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis.

• Authors report their experience using carbon dioxide for the treatment of 48 patients presenting adipose accumulations, located on the thighs, knees, and/or abdomen.

• In conclusion, use of this transcutaneous CO2 gel produced changes in the dermis similar to those observed with subcutaneous injection of CO2.

• Hyrdogel enhances gas permeation through the skin.

By the age 30, oxygen levels in your skin drop by 25% and 50% by age 40. The body naturally gets its oxygen through breathing, but factors like stress, parasympathetic and sympathetic nervous system activity and availability of CO2. The body will first utilize oxygen in the major organs and lastly, go to the skin. When the skin doesn’t get enough oxygen it becomes more prone to aging, acne, redness, irritation and age spots. 

The results testify to the fact that CO2 is a powerful inhibitor of reactive oxygen species (ROS) generation by cells (blood phagocytes and alveolar macrophages of 96 people and cells of inner organs and tissue phagocytes (of liver, brain, myocardium, lungs, kidneys, stomach, and skeleton muscles), as well as by mitochondria of the liver of 186 white mice and human tissues.

Carbon dioxide (CO2) influence in generation of active oxygen forms (AOF) in human mononuclear cells (blood phagocytes and alveolar macrophages) and animal cells (tissue phagocytes, parenchymal and interstitial cells of liver, kidney, lung, brain and stomach)

It was established that CO2 in concentrations similar to those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60 mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF generation in all the studied cells (usually reducing it 2 to 4 times). Those results were obtained not only after the direct contact of isolated cells with CO2, but also after the whole body exposure to CO2.