description
Regulation of longevity depends on genetic and environmental factors. Caloric restriction (CR), that is limiting food intake, is recognized in mammals as the best characterized and most reproducible strategy for extending lifespan. Four pathways have been implicated in mediating the CR effect. These are the insulin like growth factor (IGF-1)/insulin signaling pathway, the sirtuin pathway, the adenosine monophosphate (AMP) activated protein kinase (AMPK) pathway and the target of rapamycin (TOR) pathway. The collective response of these pathways to CR is believed to promote cellular fitness and ultimately longevity via activation of autophagy, stress defense mechanisms, and survival pathways while attenuating proinflammatory mediators and cellular growth. Furthermore, there is evidence supporting that life span extension can be achieved with pharmacologic agents that mimic the effects of caloric restriction, such as rapamycin, via mTOR signaling blockade, resveratrol, by activating SIRT1 activity, and metformin, which seems to be a robust stimulator of AMPK activity. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity

external resources
NCBI:1319989
KEGG:hsa04211
PUBMED:21779512
PUBMED:23594965
PUBMED:25654554
PUBMED:25832544
PUBMED:24997879
PUBMED:22618766
PUBMED:20336132
PUBMED:24905167
PUBMED:25601466
PUBMED:20103737
PUBMED:18692468
PUBMED:20395504
PUBMED:25824609
PUBMED:17701476
PUBMED:23939249
PUBMED:20848587
PUBMED:22983298
PUBMED:19262508
PUBMED:20357764
PUBMED:18946478
PUBMED:23061800

genes
ADCY1 , ADCY2 , ADCY3 , ADCY5 , ADCY6 , ADCY7 , ADCY8 , ADCY9 , AKT1 , AKT2 , ATF4 , BAX , CAMK4 , CAT , CREB1 , ATF2 , ATF6B , EIF4E , EIF4EBP1 , FOXO1 , FOXO3 , MTOR , HRAS , IGF1 , IGF1R , INS , INSR , IRS1 , KRAS , NFKB1 , NRAS , PIK3CA , PIK3CB , PIK3CD , PIK3R1 , PIK3R2 , PPARG , PRKAA1 , PRKAA2 , PRKAB1 , PRKAB2 , PRKACA , PRKACB , PRKACG , PRKAG1 , RELA , RHEB , RPS6KB1 , RPS6KB2 , SOD2 , STK11 , TP53 , TSC1 , TSC2 , ULK1 , IRS4 , PIK3R3 , IRS2 , KL , ADIPOQ , EIF4E2 , ATG5 , CREB5 , ATG13 , RB1CC1 , AKT3 , CREB3 , CAMKK2 , PPARGC1A , EHMT2 , SIRT1 , APPL1 , SESN1 , ADIPOR1 , PRKAG2 , PRKAG3 , RPTOR , ATG101 , CREB3L2 , ADIPOR2 , EHMT1 , SESN2 , AKT1S1 , CREB3L3 , CREB3L1 , SESN3 , CREB3L4 , ADCY4 , EIF4E1B ,