StemCell Therapy

Senescent cell removal135%2016Does not affect rotarod performance, object discrimination. Slight delay in wound closure.1Rapamycin110%2009Late-life rapamyicn treatment extends lifespan (pooled females from multiple-site NIA study)2NR105%2016Claim an increase in running distance3Catalase117%2005Mitochondrially-targeted catalase expression extended mouse lifespan compared to control4Sirt6 overexpression115%2012Sirt6-overexpression increases male mouse lifespan5Metformin106%2013In males, small but significant lifespan extension after metformin application6DN-IB110%2013Dominant negative to downregulate IKK-beta activity, delivered to hypothalamus of middle-aged mice7Klotho120%2005Overexpression under human elongation factor 1 promoter increases lifespan, slight fertility loss8S6K1118%2009KO of S6K1 extends lifspan compared to wildtype mice9p66128%1999Mutation of a p66shc, member of proto-oncogene locus SHC, extends lifespan. May be just due to cancer effect.10Lowering protein:carbohydrate ratio128%2014Varied protein, carbohydrate, and total energy levels.11Fat-specific insulin receptor knockout mice111%2003Fat-specific insulin receptor knockout mice show a significant increase in lifespan12C57BL/6 mice with NZB/OlaHsd mitochondrial mutations120%2016Same nuclear, different mitochondrial DNA.13Fasting mimicking diet112%2015FMD followed by 10 days of normal, then repeat14Rapamycin127%2014Rapamycin from 9 months of age, weight decreased ~30% at highest dose15Brain-specific Sirt1 expression116%2013Brain-specific Sirt1 expression in female mice increases lifespan over wildtype16SRT1720104%2014Start diet at 28 weeks of age, very small increase on lifespan17Spermidine111%2016Polyamine, administered in drinking water18Atg5 overexpression117%2013Transgenic mice ubiquitously expressing Atg5 (crucial for autophagasome confirmation) live longer.19Telomerase124%2012Paper showing telomerase therapy increasing life20Insulin receptor substrate null132%2008Insulin receptor substrate 1 null mouse lifespan extension in females21Snell Dwarf Mice142%2001Snell dwarf mouse paper showing life extension22Ames Dwarf Mice168%1996Original Ames dwarf mouse paper showing life extension23s-Arf/p53113%2007An extra copy of p53 and upstream regulator Arf/p16Ink4a increases lifespan24Slow growth during lactation106%2004Male mice suckled by dams fed a low-protein diet lived longer than their control cohort25Methionine restriction111%2005Methionine restriction increases mouse lifespan, here median lifespan increase in mice that survived at least 1 yr.26Rapamycin (3 months)114%2016Lifespan given from time of treatment which was 23-24 mo, used 24 mo to get percentage so this is an estimate27GHR-BP138%2000Mice deficient in growth hormone receptor / binding protein live longer (female mean, not median, lifespan shown here)28mTOR116%2013mTOR depletion extends lifespan29PTEN overexpression112%2012Overexpression of PTEN, a tumor suppressor which counteracts PI3K, extends mouse lifespan30Myc (+/-)121%2015Claim no correlation between weight and lifespan31FGF-21139%2012Hepatic-specific expression of FGF-21 (which suppresses growth hormone and reduces the production of IGF) increases lifespan, female lifespan shown here32BubR1 overexpression114%2012Kinase which localizes to kinetochore, overexpression increases lifespan33AC5 KO132%2007AC5 knockount mice lived longer than control, potentially linked to effects on cAMP production and beta-adrenergic receptor signaling.3417-alpha-estradiol112%201317-alpha-estradiol extended lifespan in males, but not females (as expected)35Acarbose122%2013Acarbose extended male more than female lifespan36TRPV1 -/-114%2014Resting exchange ratio similar at 16 mo to 3 mo37SRT2104106%2014Start diet at 28 weeks of age, very small increase if there38Hcrt-UCP2128%2006UCP2 under hypocretin promoter lowers core body temp, increases lifespan39G6PD overexpression114%2016Reduces NADP+40IGF-1 Receptor Brain KO (+/-)109%2008Brain-specific IGF-1 Receptor +/- mice live longer than WT41SURF-1 KO121%2007Mutations in SURF1, a cytochrome c oxidase assembly factor, extend lifespan. Mitochondrial.42Litter enlargemnet (CR)118%200950% enlargement of litter in first 20 days, to induce caloric restriction43mclk-1 heterozygous115%2005A heterozygous knockout of mclk1 (important in mitochondrial respiration) results in mouse lifespan extension compared to wildtype44Nordihydroguairaitic acid112%2008NDGA and aspirin extend lifespan by a little bit. Small molecule.45Aspirin108%2008NDGA and aspirin extend lifespan by a little bit. Small molecule.46SOD mimetic carboxyfullerene115%2008Carboxyfullerene, described as an SOD mimetic, increased the lifespan of treated mice compared to wildtype control47Removal of visceral fat tissue108%2008Removal of visceral fat tissue increases lifespan over control48Low glycotoxin diet112%2007Low glycotoxin (low levels of AGE's) shown to extend lifespan49Per2 (-/-)118%2016Lifespan study incomplete50Neonatal metformin120%2015Animals recieved on 3, 5, 7th day after birth - bad for females, good for males.51GHRH KO146%2013GHRH (Growth-Hormone Releasing Hormone) disruption extends lifespan, presumably through the insulin/IGF pathway axis52Sod-2 overexpresion104%2007Overexpression of SOD-2 targeted to the mitochondrion increases mouse lifespan relative to wildtype53Metallothionein cardiac-specific expression114%2006Cardiac-specific expression of antioxidant metallothionein extended the lifespan of wildtype mice compared to WT FVB control.54IGF1R(+/-)121%2013Tyrosine kinase receptor activated by IGF1/255Ink4a/Arf/Ink4b116%2009Encodes 2 CDKs (p16 and p15), and Arf (upstream of p53)56Adult-onset Ghr (-/-)100%2016Male mice have >2x higher insulin than female mice57Ovary Transplantation117%2003Original paper showing that transplantation of young ovaries into old animals could result in lifespan increase58UCP-1 transgenic111%2007Transgenic mice with skeletal muscle-specific UCP1 had increased longevity. Small increase if there.59PAPP131%2010Knockout of PAPP-A (which enhances IGF-1 activity by degrading the inhibitory IGF-binding protein) increases lifespan over wildtype, female lifespan shown here60CR diet with lard132%201540% decrease starting at 4 months61loss of function of Riib (PKA subunit)114%2009Knockout of RIIbeta, a subunit of PKA, increased lifespan in mice compared to wildtype62Myostatin (+/-)109%2015Knockout induces double-muscle mice63Akt1 +/-113%2013Haploinsufficiency of Akt1 increases mouse lifespan relative to wildtype. Insulin/IGF-1 pathway.64miR-17117%2014Not clear if there is a main function for miR-1765NDGA111%2015Makes up ~12.5% of the dry weight of leaves66FAT10ko119%2014Ubiquitin-like protein which can signal for protein to go to proteasome.67Intranasal Hsp70116%2015Seemed to extend lifespan when started at 17 months68RasGRF1(-/-)120%2011Ras-guanine nucleotide exchange factor (Ras-GRF1) -/- mice displayed increased lifespan compared to wildtype.69Lmna-Lcs (Lamin C alone)113%2014Body weight and tumor incidence increase in mice expressing only Lamin-C70Cisd2 overexpression119%2011Cisd2 transgenic mice (expressing more of it) lived longer than wildtype. Cisd2 is a transmembrane protein expressed on the mitochondrial outer membrane and associated with a human longevity locus.71metoprolol110%2013Administration of the beta-adrenerginc receptor blocker metoprolol to mice increased lifespan compared to wildtype72nebivolol106%2013Administration of the beta-adrenerginc receptor blocker nebivolol to mice increased lifespan compared to wildtype73uPA (in ocular lens/CNS nerve cells)118%1997uPA expression under alpha-crystallin promoter increases lifespan, small/eat less74MIF-1 KO116%2010MIF-1 knockout mutant (T-cell derived cytokine) extends lifespan75mGsta4-null113%2009Enzyme protects against lipid peroxidation, weird that less of its activity might increase lifespan76Muscle-specific GHRKO109%2015Knockout under muscle creatinine kinase promoter77CAM-(1A)AR mice110%2011Mice with a constitutively active mutant form of the alpha1-adrenergic receptor (CAM-alpha1aAR) lived longer than wildtype control78Cardiac-specific catalase overexpression113%2007Overexpression of catalase specifically in the heart in mice79Icariin108%2015Flavonoid80miR-29 brain-specific KO112%2016miR-29 highly expresed in brain during development81Bi-maternal mice128%2010Mice prepared to be bi-maternal were found longer-lived than their normal cohort82RNase-L(-/-)127%2007Knockout of RNase-L, which accelerates cell senescence when expressed, increases lifespan in mice compared to wildtype83hMTH1-Tg116%2013Express high levels of hMTH1 hydrolase, thought to degrade 8-oxodGTP and 8-oxoGTP. Oxidative stress.84DGAT-1 -/-126%2012Knockout of DGAT1, which catalyzes triglyceride synthesis, extends mouse lifespan relative to wildtype85IGFBP-2 overexpression105%2016Proteins bind IGF1/2, degraded during pregnancy, delay in sexual maturity86PAPP-A on high-fat diet105%2015Males chosen so no adverse developmental effect on fat depots87clk-1(-/-) with clk-1 transgene128%2014clk-1 functions in ubiquinone synthesis, but levels weren't very affected.88AgRP -/-110%2006Neuropeptide that is appetite stimulator, overexpression leads to hyperphagia and obesity.89Bone marrow transplantation106%2013Bone marrow transplantation from young to old mice was claimed to extend lifespan90Young blood injections94%2014Resulted in decreased lifespan91Nas(-/-) mice125%2011Hyposulfatemic NaS1 null mice (Nas1 -/-) had an increased lifespan compared to wildtype control.92Cyclophilin D (+/-)119%2017Decrease in maximum lifespan93PAPP-A in adults120%2017Tamoxifen-induced knockdown94Mtbp (+/-)120%2016Rotarod, open field, blood glucose, insulin, IGF-1 were the same.95

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Longevity FAQ Laura Deming

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