Panorama Research Institute, Sunnyvale, California, USA.
Regenerative Sciences Institute, Sunnyvale, California, USA.
Rejuvenation Res. 2021 Apr;24(2):158-163. doi: 10.1089/rej.2021.0014.
Modest modulation of oxygen intake, either by inducing mild intermittent hypoxia or hyperoxia appears to induce modest rejuvenative changes in mammals, in part, by activating key regulator hypoxia-induced factor 1a (HIF-1a). Interestingly both lower oxygen and transient higher oxygen levels induce this hypoxia regulator. Hyperbaric oxygen induces HIF-1a by the hyperoxic-hypoxic paradox that results from an overinduction of protective factors under intermittent hyperoxic conditions, leading to a state somewhat similar to that induced by hypoxia. A key difference being that SIRT1 is induced by hyperoxia, whereas it is reduced during hypoxia by the activity of HIF-1a. In a recent report, a small clinical trial employing 60 sessions of intermittent hyperbaric oxygen therapy (HBOT) studying old humans resulted in increased mean telomere length of immune cells including B cells, natural killer cells, T helper, and cytotoxic T lymphocytes. Moreover, there was a reduction in CD28 senescent T helper and cytotoxic T cells. In a parallel report, HBOT has been reported to enhance cognition in older adults, especially attention and information processing speed through increased cerebral blood flow (CBF) in brain regions where CBF tends to decline with age. The durability of these beneficial changes is yet to be determined. These preliminary results require follow-up, including more extensive characterization of changes in aging-associated biomarkers. An interesting avenue of potential work is to elucidate potential connections between hypoxia and epigenetics, especially the induction of the master pluripotent regulatory factors, which when expressed transiently have been reported to ameliorate some aging biomarkers and pathologies.
适度调节氧气摄入，无论是通过诱导轻度间歇性缺氧还是过度供氧，似乎都能通过激活关键调节因子缺氧诱导因子 1a（HIF-1a），使哺乳动物产生适度的再生变化。有趣的是，较低的氧气和短暂的较高氧气水平都会诱导这种缺氧调节剂。高压氧通过缺氧-缺氧悖论诱导 HIF-1a，这是由于间歇性高氧条件下保护性因素过度诱导，导致状态与缺氧诱导的状态有些相似。一个关键的区别是，SIRT1 被过度供氧诱导，而在缺氧条件下，它被 HIF-1a 的活性所降低。在最近的一项报告中，一项采用 60 次间歇性高压氧治疗（HBOT）的小型临床试验研究了老年人，结果显示免疫细胞（包括 B 细胞、自然杀伤细胞、辅助性 T 细胞和细胞毒性 T 淋巴细胞）的平均端粒长度增加。此外，CD28 衰老的辅助性 T 细胞和细胞毒性 T 细胞减少。在一项平行报告中，HBOT 已被报道可通过增加大脑区域的脑血流量（CBF）来增强老年人的认知能力，特别是注意力和信息处理速度，而 CBF 随着年龄的增长往往会下降。这些有益变化的持久性还有待确定。这些初步结果需要进一步跟进，包括更广泛地描述与衰老相关的生物标志物的变化。一个有趣的潜在工作方向是阐明缺氧与表观遗传学之间的潜在联系，特别是诱导主要多能调节因子，当这些因子短暂表达时，据报道可以改善一些衰老生物标志物和病理。
