TABLE 2.

The effect of hyperoxia on aging markers in cell lines.

Author and year	Cell line	Hyperoxia protocol	Aging markers	Results	Conclusion	Safety issues (oxygen toxicity)
Godman et al. (2010)	HMEC-1	100% O2 at 2.4 ATA for 1 h	Antioxidant gene expression in Nrf2, Integrin, and ERK/MAPK pathways	The HSPA1A, HMOX1, and MT1X genes were upregulated, and collectively can provide protection from metabolic, proteotoxic, and oxidative forms of stress. ERK/MAPK signaling, including the activation of a number of immediate early genes can potentially influence apoptotic signaling. Endothelial cell viability in the HBO-treated cultures was significantly increased	The data indicate that hyperbaric oxygen can induce protection against oxidative insults in endothelial cells and may provide an easily administered hormetic treatment to help promote healthy aging	HBO is a relatively low-risk procedure that could be effectively applied as a broader preventative regimen to reduce the effects of aging
Pomatto et al. (2019)	MEFs	40% O2 for 2 weeks	Nrf2 signal transduction pathway	Hyperoxia increased baseline levels of Nrf2 and multiple transcriptional targets (20S Proteasome, Immunoproteasome, Lon protease, NQO1, and HO-1)	Changes the balance of Nrf2, Bach1, and c-Myc levels may account for dysregulation of stress responses and adaptive homeostasis during chronic hyperoxia and in aging	Not reported
			Nrf2 inhibitors (Bach1 and c-Myc)	Bach1 and c-Myc were strongly elevated by hyperoxia and appeared to exert a ceiling on Nrf2 signaling. Bach1 and c-Myc also increase during aging and may thus be the mechanism by which adaptive homeostasis is compromised with age
			Cellular ability to adapt to signaling levels (1.0 μM) of H2O4	Hyperoxia resulted in loss of cellular ability to adapt to signaling levels (1.0 μM) of H2O2

HMEC-1, Human microvascular endothelial cell line; MEFs, Mouse embryonic fibroblasts; HSPA1A, 70- kilodalton heat shock protein; HMOX1, heme oxygenase 1; MT1X, metallothionein 1X.