Table 1.

Human genes and their orthologues associated with the longevity of lifespan. The main physiological roles of and reported association with life threatening diseases have been discussed for each gene.

Sr. No.	Gene	Protein	Main Physiological Role	Change with Age or Abnormility	Reference
1	APOE	Apolipoprotein E	Odulation of cholesterol balance Aggregability of platelets Proliferation of lymphocytes	Pathogenesis of atherosclerosis and in Alzheimer’s disease	[25,26,27]
2	P53	Tumor protein p53	Tumor suppression Transcription activation	Cancer	[28,29,30]
3	SIRT1	Sirtuin 1 protein	Metabolism and energy homeostasis DNA damage response	Aging, cancer Slow lipid metabolism	[31,32,33,34,35]
4	DAF-16	FOXO1 transcription factor	Transcription factor	Cell cycle arrest, apoptosis	[36,37,38]
5	CHRNA3	Cholinergic receptor nicotinic alpha 3 subunit	Response to foreign materials such as nicotine and alcohol Nervous system	Addiction to alcohol/cocaine Decline in nerve response	[39,40]
6	SH2B3	SH2B adaptor protein 3	Multifunctional adopter protein	Cancer, age dependent Insulin resistance	[41,42,43,44,45]
7	CDKN2A	Cyclin dependent kinase inhibitor 2A	Cell cycle control	Diabetes type 2, obesity, adipose tissue browning, cardiac dystrophy	[46,47,48,49,50,51]
8	ELOVL2	Elongation of very-long-chain fatty acids-like 2	DHA (Docosahexaenoic acid) synthesis, lipid storage	Glucolipotoxicity-induced apoptosis	[52,53,54,55]
9	WRN	Werner protein	DNA protection against oxidative stress damage, genome stability	Premature aging disease, cataracts, atherosclerosis, osteoporosis, and cancer	[56,57,58,59,60]
10	PON1	Paraoxonase 1	Detoxifies Hcy-thiolactone in human blood and reduces chances of atherosclerosis	Cardiovascular disease	[61,62,63,64]
11	SOD2	Superoxide dismutase 2	Fights against oxidative stress ROS scavenger	Alzeimer’s disease, diabetes, cardiac complications	[65,66,67,68]
12	LMNA	Lamin A protein	Regulation of antioxidant associated genes, Impaired protein dysregulation Cardiomyocites function	Accelerated aging process	[69,70,71,72]
13	CETP	Cholesteryl ester transfer protein	Lipoprotein metabolism	Cardiovascular diseases	[73,74,75,76]
14	APOC3	Apolipoprotein C3	Lipid transport Glucose metabolism Neuronal signaling	Insulin resistance Coronary artery calcium and AD	[77,78,79,80]
15	MTP	Microsomal triglyceride transfer protein	Multifunctional protein, cholesterol synthesis, lipd transport lipid and lipoprotein homeostasis	Metabolic diseases	[81,82,83]
16	PIK3CA	Phosphatidylinositol 3-kinase (PI3K).	Neuronal differentiation and survival	Cancer	[84,85,86,87]
17	DAF-2	Insulin-like growth factor 1 (IGF-1) receptor	Anabolic and mitogenic activity	Cancer	[88,89,90,91]
18	PIMT	Protein-L-isoaspartyl methyltransferase	Intrecellular signal transduction	Fatal epilepsy	[92,93,94]
19	GH1	Growth hormone	Growth and development Interaction with insulin-like growth factor	Aging Chronic kidney disease	[95,96,97,98,99,100]
20	KLOTHO	Protein alpha-klotho	Aging suppression Organ protection Phosphate homeostasis Vascular physiology	Chronic kidney and vascular disease,	[101,102,103,104,105,106,107,108]
21	CREB	cAMP-response element binding protein	Neuronal protection, plasticity and memory Triglyceride metabolism	Alzheimer’s disease	[109,110,111,112,113]
22	MAPK	Mitogen-activated protein kinase	Multiple physiological functions Innate immune response Stress signaling	Alzheimer’s disease Parkinson’s disease Cardiac hypertrophy	[114,115,116,117,118,119]
23	EGFR	epidermal growth factor receptor	Nervous system physiology Actin remodeling in sperm capacitation	Cancer	[120,121,122,123,124]
24	NF-kB	Nuclear factor kappa B	Immune response modulator/activator Depression	Coronary artery disease Cancer and immune diseases	[125,126,127,128,129,130]
25	PLC-β	Phospholipase C beta	Signal transduction Brain activity Breast cancer suppression	Neurodegenerative disease; metastasis	[131,132,133,134]
26	MSR-A	Methionine sulfoxide reductase A	Repair of of oxidized methionine in proteins Protects against oxidative stress	Neurodegenerative diseases, cystic fibrosis, neurological disorders, cancer	[135,136,137,138]
27	MEMO1	Mediator of cell motility 1	Cell migration (neuronal cells), Organismal development Central nervous system	Cancer Neurological disorders	[139,140]
28	NEIL1	Nei like DNA Ggycosylase 1	Neurogenesis DNA repair Neuronal protection against oxidative stress	Alzheimer’s disease	[141,142,143]
29	PPARγ2	Peroxisome proliferator-activated receptor gamma 2	Adipogenesis Lipid metabolism	Cardiovascular diseases	[144,145,146,147]
30	EIF3K	Eukaryotic translation initiation factor 3 subunit K	Regulation of apoptosis in C. elegans	Lifespan extension in C. elegans	[148,149,150]
31	ATM	ATM serine/threonine kinase	Cellular response to genotoxic stress	Lymphoid malignancies Coronary artery disease	[151,152,153,154]
32	BCL2	B-cell lymphoma 2	Multiple functions neuronal activity autophagy calcium homeostasis	Huntington’s disease Chronic obstructive pulmonary disease	[155,156,157]
33	CDC42	Cell division cycle 42	Regulation of mammary gland functioning	Genomic instability Aging	[158,159,160,161,162]
34	DGAT1	Diacylglycerol O -acyltransferase 1	Triglyceride metabolism Promote LDL levels	Congenital diarrheal disorder	[163,164,165,166]
35	EGR1	Early growth response 1	Complex response to stress	Cancer	[167,168,169,170]
36	FGF23	Fibroblast growth factor 23	Phosphate and vitamin D metabolism	Chronic kidney disease	[171,172,173]
37	FGF21	Fibroblast growth factor 21	lipolysis in adipose tissue	Cardiovascular disease	[174,175,176,177,178]
38	FN3KRP	Fructosamine 3 kinase related protein	Cell maintenance and viability Longevity of lifespan	-	[179,180]
39	PGP	Phosphoglycolate phosphatase	Intermediary metabolism	Cardiometabolic diseases	[179,180,181]
40	IRS1	Insulin receptor substrate 1	Insulin signaling	Coronary artery disease Tau pathology in alzheimer’s disease	[182,183,184,185,186]
41	BMI1	Polycomb complex protein BMI-1	Gene silencing Regulation of chromatin structure Cellular bioenergetics DNA damage response	Hematologic malignancies	[187,188,189,190,191]
42	NRG-1	Neuregulin 1	Signaling in the cardiovascular system Maintenance of muscle spindles	Schizophrenia	[192,193,194,195,196]
43	STAT	Signal transducer and activator of transcription	Multiple roles Cell signaling	Autoimmune diseases Cancers	[197,198,199,200,201]
44	E2F1	E2F Transcription Factor 1	Innate immune response Regulation of metabolism	Cancers	[202,203,204,205,206]
45	VEGF-A	Vascular endothelial growth factor A	Cell signale transduction	Cancers	[207,208,209]
46	XME	Xenobiotic metabolizing enzymes	Breakdown of xenobiotic substances	-	[210,211,212,213]
47	MYC	Myc proto-oncogene protein	Maintains regular physiology Tissue repair Placenta development Immune response	Cancer	[214,215,216,217]
48	CXCR4	C-X-C chemokine receptor type 4	Bone marrow physiology	Cancer	[218,219,220]
49	SIR-2	Silent information regulator 2	Extends lifespan in Drosophila Human cardiac contractile Suppress neurodegeneration	Neurodegenerative disease Cardiac failure	[221,222,223,224,225]
50	ERK	Extracellular signal-regulated kinase	Cell signaling	Leukemia	[226,227]
51	SLC31		Copper transporters	Immune dysfunction Multiple diseases	[228]