Table 1.

Mechanisms of H₂ in multiple ageing-related diseases.

Diseases		Effect of H2	References (cell/animal/human)
Neurodegenerative diseases	Alzheimer's disease	Inhibits JNK, nuclear NF-κB, IL-6, TNF-α, and IL-1β; inhibits MAD and 8-OHdG; upregulates Sirt1-FoxO3a; and ERβ-BDNF signaling.	[132] Sprague-Dawley rats; [133] Sprague-Dawley male rats; [134] SK-N-MC cells; and [135] APPswe/PS1dE9 mice.
	Parkinson's disease	Prevents dopaminergic neuron loss; decreases 8-OHdG and 4-HNE; and hermetic regulation by increasing 8-OHdG.	[138] Sprague-Dawley rats; [139] C57BL/6J mice; and [145] human.
	Heart	Activates PINK1/Parkin-mediated mitophagy; restores ETC enzyme activity; increases ATP production; suppresses NADPH oxidase; inhibits NF-κB; and inhibits p53-mediated apoptosis.	[38] Wistar rats; [116] Wistar rats and H9C2 cells; [152] spontaneously hypertensive rats and Wistar-Kyoto rats; and [154] Sprague-Dawley rats.
	Blood vessels	Decreases oxidized LDL; improves HDL function and glucose metabolism; activates Sirt1-mediated autophagy; and modulates NO bioavailability.	[12] human; [64] RAW264.7 cell; [152] spontaneously hypertensive rats and Wistar-Kyoto rats; [159] human; and [160] human.
	COPD	Alleviates small-airway remodeling and goblet-cell hyperplasia; restores static lung compliance; reduces inflammatory cells in BALF; and decreases oxidative DNA damage.	[51] senescence marker protein 30 knockout mice; [169] C57BL mice; and [170] Sprague-Dawley rats.
	Pulmonary fibrosis	Reduces ROS content; inhibits TGF-β1and EMT; increases E-cadherin; and decreases 8-OHdG-positive cell numbers.	[172] Wistar rats; [173] D1CC transgenic mice.
Metabolic diseases	DM	Improves obesity and lipid and glucose metabolism; improves insulin resistance; increases HFGF21; and inhibits peripheral blood IL-1β mRNA.	[12, 176, 177] human; [176] Sprague-Dawley rats, C57BL/6 mice, and db/db mice; and [177] Sprague-Dawley rats.
Cancer		Inhibits ROS, apoptosis, and inflammation in lesion tissue; downregulates chromosome 3; enhances anticancer effects; alleviates side effects of anticancer therapies; modulates immune function; and restores exhausted CD8+ T cells.	[127] A549 and H1975 cells; [180] C57BL/6 mice; [182] mouse colon carcinoma cell line and BALB/c mice; [185] C57BL/6J mice and human lung cancer cell lines A549; [186] Wistar albino rats; [187] human; and [189] human.