Table 1.

Interactive properties of humanin/MDPs in non-ocular tissues.

Condition	Cell/Tissue	Species	MDP family member	Findings	Refs
Myocardial fibrosis	Cardiac tissue	Mice	HNG	Attenuation of myocardial fibrosis	[84]
Cardiomyopathy	Cardiac tissue	Mice	HNG	Cardiac protection and preserved mitochondrial function.	[92]
Cardiac ischemia-reperfusion (I/R) injury induced brain dysfunction	Cardiac tissue, Brain	Rats	HNG	Attenuated mitochondrial dysfunction and reduced brain susceptibility to apoptosis.	[93]
Myocardial I/R injury	Cardiac tissue	Rats	HNG	Decreased cardiac arrhythmia, myocardial infarct size, mitochondrial dysfunction, and left ventricular dysfunction.	[94]
Cardiovascular disease	Cardio myoblasts	Mice	HNG	Removal of abnormal proteins via chaperone-mediated autophagy.	[91]
Myocardial ischemia and reperfusion	Myocardium cell line, cardiac tissue	Mice	HNG	Cardio protection, decrease in infarct size and improvement in ventricular function	[95]
Cerebrovascular diseases	Cardiac tissue. Neuronal cells	Mice	HNG	Removal of abnormal proteins via chaperone-mediated autophagy	[91]
Cardiovascular disease	Platelets	Mice	HNG	Attenuated cremaster arterial thrombus formation	[96]
Aging	C. elegans	Worm	HN	Increased lifespan	[97]
Cancer	Blood plasma, testes	Mice	HNG	Cytoprotection of germ cells and leukocytes and non-cancerous cells in tumor-bearing mice.	[98]
Neuroblastoma or medulloblastoma	Growth plate tissues/metatarsal bones/tumor xenografts	Human, Mice	HNG	Prevention of bone growth impairment and chondrocyte apoptosis	[99]
Cancer	Breast cancer cells	Human, Mice	HN	Pro-tumoral effects	[100]
Cancer and fertility	Blood, liver, spleen, testes	Mice	HNG	Amelioration of chemotherapy-induced germ cell apoptosis; WBC and granulocyte loss.	[101]
Neurodegenerative diseases.	Neuroblastoma cell line (SH-SY5Y).	Human	HN-silver Nanoparticles	Neuroprotection	[102]
Alzheimer's disease	Cortical neurons	Rats	HN	Attenuation of NMDA- excitotoxicity, improvement of mitochondrial function	[103,104]
Alzheimer's disease	Brain	Mice	HNG	Improved cognitive function	[105,106]
Alzheimer's disease	Brain	Rats	HNG	Reversal of impairment of spatial memory	[107]
Alzheimer's disease	Brain	Mice	HNG	Decreased Aβ level and ameliorated cognitive impairment.	[108]
Alzheimer's disease	Brain	Rats	HN	Amelioration of memory deficits induced by Aβ (1-42).	[109]
Glucocorticoid-induced Bone growth impairment	Metatarsal bones/growth plate biopsies/chondrocytes	Rats, Human, HN-Tg mice	HN	Prevention of GC-induced growth impairment in cultured bones	[110]
Arthritis	Articular and growth plate cartilage	Mice	HNG	Decreased chondrocyte apoptosis	[110]
Stroke	Brain	Mice	HN	Reduction of neurological deficits, and improved hematoma clearance	[83]
Endothelial dysfunction	Umbilical vein endothelial cells	Human	HNG	Decrease in lipid aggregation and apoptosis	[76]
Obesity	Plasma	Mice	HNG	Regulation of glutathione and sphingolipid metabolism	[111]
Atherosclerosis/diabetes	Umbilical vein endothelial cells	Human	HN	Prevention of hyperglycemia-associated endothelial dysfunction	[112]
Diabetes	Umbilical vein endothelial cells	Human	HNG	Reduction in apoptosis induced by high glucose	[113]
Diabetes	Beta-cells/NOD mice	Mice	HN	Decreased apoptosis and delayed onset of diabetics	[79]
Diabetes	Liver	Rats	HNGF6A	Lowering of blood glucose	[78]
Atherosclerosis	Proximal aorta	Mice	HNGF6A	Improved endothelial function and impaired progression of atherosclerosis	[114]
Age-related diseases	NIT-1 murine β-cells, prostate carcinoma cell line	Mice, human	SHLP2	Increased glucose uptake and suppressed hepatic glucose production.	[59]
Obesity	Plasma	Mice	SHLP2	Regulation of glutathione and sphingolipid metabolism	[111]
Diet-induced obesity	HEK293, HeLa cells, Liver, skeletal muscle	Human, Mice	MOTS-c	Reduction of obesity	[58]
HFD-induced hyperinsulinemia	Liver	Mice	MOTS-c	Attenuated hyperinsulinemia	[58]
Ovariectomy‐induced osteoporosis	Bone	Mice	MOTS-c	Alleviated bone loss	[115]
Osteolysis	Primary bone marrow macrophages, bone	Mice	MOTS-c	Alleviated bone erosion and inflammation.	[116]
Hypothermia	Plasma, liver	Mice	MOTS-c	Increased activation of adipose thermogenesis	[117]
Bone fracture	Bone Marrow Mesenchymal Stem Cells	Rats	MOTS-c	Accelerated bone fracture healing	[118]
Endothelial dysfunction	Aortic rings, renal artery stenosis	Rats, mice	MOTS-c	Improved endothelial function	[119]