Longevity FAQ: A beginner's guide to longevity research
Longevity FAQ — Laura Deming

		
			
				95 things that make mice live longer
				Ordered by citations/year
			
			
				
					Intervention
				Median lifespan increase (treated/control)
				Year Published
				Notes
				Reference
				
			
			
				
				
					Senescent cell removal
					135%
					2016
					Does not affect rotarod performance, object discrimination. Slight delay in wound closure.
					1
				
			

				
					Rapamycin
					110%
					2009
					Late-life rapamyicn treatment extends lifespan (pooled females from multiple-site NIA study)
					2
				
			

				
					NR
					105%
					2016
					Claim an increase in running distance
					3
				
			

				
					Catalase
					117%
					2005
					Mitochondrially-targeted catalase expression extended mouse lifespan compared to control
					4
				
			

				
					Sirt6 overexpression
					115%
					2012
					Sirt6-overexpression increases male mouse lifespan
					5
				
			

				
					Metformin
					106%
					2013
					In males, small but significant lifespan extension after metformin application
					6
				
			

				
					DN-IκBα
					110%
					2013
					Dominant negative to downregulate IKK-beta activity, delivered to hypothalamus of middle-aged mice
					7
				
			

				
					Klotho
					120%
					2005
					Overexpression under human elongation factor 1α promoter increases lifespan, slight fertility loss
					8
				
			

				
					S6K1
					118%
					2009
					KO of S6K1 extends lifspan compared to wildtype mice
					9
				
			

				
					p66
					128%
					1999
					Mutation of a p66shc, member of proto-oncogene locus SHC, extends lifespan. May be just due to cancer effect.
					10
				
			

				
					Lowering protein:carbohydrate ratio
					128%
					2014
					Varied protein, carbohydrate, and total energy levels.
					11
				
			

				
					Fat-specific insulin receptor knockout mice
					111%
					2003
					Fat-specific insulin receptor knockout mice show a significant increase in lifespan
					12
				
			

				
					C57BL/6 mice with NZB/OlaHsd mitochondrial mutations
					120%
					2016
					Same nuclear, different mitochondrial DNA.
					13
				
			

				
					Fasting mimicking diet
					112%
					2015
					FMD followed by 10 days of normal, then repeat
					14
				
			

				
					Rapamycin
					127%
					2014
					Rapamycin from 9 months of age, weight decreased ~30% at highest dose
					15
				
			

				
					Brain-specific Sirt1 expression
					116%
					2013
					Brain-specific Sirt1 expression in female mice increases lifespan over wildtype
					16
				
			

				
					SRT1720
					104%
					2014
					Start diet at 28 weeks of age, very small increase on lifespan
					17
				
			

				
					Spermidine
					111%
					2016
					Polyamine, administered in drinking water
					18
				
			

				
					Atg5 overexpression
					117%
					2013
					Transgenic mice ubiquitously expressing Atg5 (crucial for autophagasome confirmation) live longer.
					19
				
			

				
					Telomerase
					124%
					2012
					Paper showing telomerase therapy increasing life
					20
				
			

				
					Insulin receptor substrate null
					132%
					2008
					Insulin receptor substrate 1 null mouse lifespan extension in females
					21
				
			

				
					Snell Dwarf Mice
					142%
					2001
					Snell dwarf mouse paper showing life extension
					22
				
			

				
					Ames Dwarf Mice
					168%
					1996
					Original Ames dwarf mouse paper showing life extension
					23
				
			

				
					s-Arf/p53
					113%
					2007
					An extra copy of p53 and upstream regulator Arf/p16Ink4a increases lifespan
					24
				
			

				
					Slow growth during lactation
					106%
					2004
					Male mice suckled by dams fed a low-protein diet lived longer than their control cohort
					25
				
			

				
					Methionine restriction
					111%
					2005
					Methionine restriction increases mouse lifespan, here median lifespan increase in mice that survived at least 1 yr.
					26
				
			

				
					Rapamycin (3 months)
					114%
					2016
					Lifespan given from time of treatment which was 23-24 mo, used 24 mo to get percentage so this is an estimate
					27
				
			

				
					GHR-BP
					138%
					2000
					Mice deficient in growth hormone receptor / binding protein live longer (female mean, not median, lifespan shown here)
					28
				
			

				
					mTOR
					116%
					2013
					mTOR depletion extends lifespan
					29
				
			

				
					PTEN overexpression
					112%
					2012
					Overexpression of PTEN, a tumor suppressor which counteracts PI3K, extends mouse lifespan
					30
				
			

				
					Myc (+/-)
					121%
					2015
					Claim no correlation between weight and lifespan
					31
				
			

				
					FGF-21
					139%
					2012
					Hepatic-specific expression of FGF-21 (which suppresses growth hormone and reduces the production of IGF) increases lifespan, female lifespan shown here
					32
				
			

				
					BubR1 overexpression
					114%
					2012
					Kinase which localizes to kinetochore, overexpression increases lifespan
					33
				
			

				
					AC5 KO
					132%
					2007
					AC5 knockount mice lived longer than control, potentially linked to effects on cAMP production and beta-adrenergic receptor signaling.
					34
				
			

				
					17-alpha-estradiol
					112%
					2013
					17-alpha-estradiol extended lifespan in males, but not females (as expected)
					35
				
			

				
					Acarbose
					122%
					2013
					Acarbose extended male more than female lifespan
					36
				
			

				
					TRPV1 -/-
					114%
					2014
					Resting exchange ratio similar at 16 mo to 3 mo
					37
				
			

				
					SRT2104
					106%
					2014
					Start diet at 28 weeks of age, very small increase if there
					38
				
			

				
					Hcrt-UCP2
					128%
					2006
					UCP2 under hypocretin promoter lowers core body temp, increases lifespan
					39
				
			

				
					G6PD overexpression
					114%
					2016
					Reduces NADP+
					40
				
			

				
					IGF-1 Receptor Brain KO (+/-)
					109%
					2008
					Brain-specific IGF-1 Receptor +/- mice live longer than WT
					41
				
			

				
					SURF-1 KO
					121%
					2007
					Mutations in SURF1, a cytochrome c oxidase assembly factor, extend lifespan. Mitochondrial.
					42
				
			

				
					Litter enlargemnet (CR)
					118%
					2009
					50% enlargement of litter in first 20 days, to induce caloric restriction
					43
				
			

				
					mclk-1 heterozygous
					115%
					2005
					A heterozygous knockout of mclk1 (important in mitochondrial respiration) results in mouse lifespan extension compared to wildtype
					44
				
			

				
					Nordihydroguairaitic acid
					112%
					2008
					NDGA and aspirin extend lifespan by a little bit. Small molecule.
					45
				
			

				
					Aspirin
					108%
					2008
					NDGA and aspirin extend lifespan by a little bit. Small molecule.
					46
				
			

				
					SOD mimetic carboxyfullerene
					115%
					2008
					Carboxyfullerene, described as an SOD mimetic, increased the lifespan of treated mice compared to wildtype control
					47
				
			

				
					Removal of visceral fat tissue
					108%
					2008
					Removal of visceral fat tissue increases lifespan over control
					48
				
			

				
					Low glycotoxin diet
					112%
					2007
					Low glycotoxin (low levels of AGE's) shown to extend lifespan
					49
				
			

				
					Per2 (-/-)
					118%
					2016
					Lifespan study incomplete
					50
				
			

				
					Neonatal metformin
					120%
					2015
					Animals recieved on 3, 5, 7th day after birth - bad for females, good for males.
					51
				
			

				
					GHRH KO
					146%
					2013
					GHRH (Growth-Hormone Releasing Hormone) disruption extends lifespan, presumably through the insulin/IGF pathway axis
					52
				
			

				
					Sod-2 overexpresion
					104%
					2007
					Overexpression of SOD-2 targeted to the mitochondrion increases mouse lifespan relative to wildtype
					53
				
			

				
					Metallothionein cardiac-specific expression
					114%
					2006
					Cardiac-specific expression of antioxidant metallothionein extended the lifespan of wildtype mice compared to WT FVB control.
					54
				
			

				
					IGF1R(+/-)
					121%
					2013
					Tyrosine kinase receptor activated by IGF1/2
					55
				
			

				
					Ink4a/Arf/Ink4b
					116%
					2009
					Encodes 2 CDKs (p16 and p15), and Arf (upstream of p53)
					56
				
			

				
					Adult-onset Ghr (-/-)
					100%
					2016
					Male mice have >2x higher insulin than female mice
					57
				
			

				
					Ovary Transplantation
					117%
					2003
					Original paper showing that transplantation of young ovaries into old animals could result in lifespan increase
					58
				
			

				
					UCP-1 transgenic
					111%
					2007
					Transgenic mice with skeletal muscle-specific UCP1 had increased longevity. Small increase if there.
					59
				
			

				
					PAPP
					131%
					2010
					Knockout of PAPP-A (which enhances IGF-1 activity by degrading the inhibitory IGF-binding protein) increases lifespan over wildtype, female lifespan shown here
					60
				
			

				
					CR diet with lard
					132%
					2015
					40% decrease starting at 4 months
					61
				
			

				
					loss of function of Riib (PKA subunit)
					114%
					2009
					Knockout of RIIbeta, a subunit of PKA, increased lifespan in mice compared to wildtype
					62
				
			

				
					Myostatin (+/-)
					109%
					2015
					Knockout induces double-muscle mice
					63
				
			

				
					Akt1 +/-
					113%
					2013
					Haploinsufficiency of Akt1 increases mouse lifespan relative to wildtype. Insulin/IGF-1 pathway.
					64
				
			

				
					miR-17
					117%
					2014
					Not clear if there is a main function for miR-17
					65
				
			

				
					NDGA
					111%
					2015
					Makes up ~12.5% of the dry weight of leaves
					66
				
			

				
					FAT10ko
					119%
					2014
					Ubiquitin-like protein which can signal for protein to go to proteasome.
					67
				
			

				
					Intranasal Hsp70
					116%
					2015
					Seemed to extend lifespan when started at 17 months
					68
				
			

				
					RasGRF1(-/-)
					120%
					2011
					Ras-guanine nucleotide exchange factor (Ras-GRF1) -/- mice displayed increased lifespan compared to wildtype.
					69
				
			

				
					Lmna-Lcs (Lamin C alone)
					113%
					2014
					Body weight and tumor incidence increase in mice expressing only Lamin-C
					70
				
			

				
					Cisd2 overexpression
					119%
					2011
					Cisd2 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.
					71
				
			

				
					metoprolol
					110%
					2013
					Administration of the beta-adrenerginc receptor blocker metoprolol to mice increased lifespan compared to wildtype
					72
				
			

				
					nebivolol
					106%
					2013
					Administration of the beta-adrenerginc receptor blocker nebivolol to mice increased lifespan compared to wildtype
					73
				
			

				
					uPA (in ocular lens/CNS nerve cells)
					118%
					1997
					uPA expression under alpha-crystallin promoter increases lifespan, small/eat less
					74
				
			

				
					MIF-1 KO
					116%
					2010
					MIF-1 knockout mutant (T-cell derived cytokine) extends lifespan
					75
				
			

				
					mGsta4-null
					113%
					2009
					Enzyme protects against lipid peroxidation, weird that less of its activity might increase lifespan
					76
				
			

				
					Muscle-specific GHRKO
					109%
					2015
					Knockout under muscle creatinine kinase promoter
					77
				
			

				
					CAM-α(1A)AR mice
					110%
					2011
					Mice with a constitutively active mutant form of the alpha1-adrenergic receptor (CAM-alpha1aAR) lived longer than wildtype control
					78
				
			

				
					Cardiac-specific catalase overexpression
					113%
					2007
					Overexpression of catalase specifically in the heart in mice
					79
				
			

				
					Icariin
					108%
					2015
					Flavonoid
					80
				
			

				
					miR-29 brain-specific KO
					112%
					2016
					miR-29 highly expresed in brain during development
					81
				
			

				
					Bi-maternal mice
					128%
					2010
					Mice prepared to be bi-maternal were found longer-lived than their normal cohort
					82
				
			

				
					RNase-L(-/-)
					127%
					2007
					Knockout of RNase-L, which accelerates cell senescence when expressed, increases lifespan in mice compared to wildtype
					83
				
			

				
					hMTH1-Tg
					116%
					2013
					Express high levels of hMTH1 hydrolase, thought to degrade 8-oxodGTP and 8-oxoGTP. Oxidative stress.
					84
				
			

				
					DGAT-1 -/-
					126%
					2012
					Knockout of DGAT1, which catalyzes triglyceride synthesis, extends mouse lifespan relative to wildtype
					85
				
			

				
					IGFBP-2 overexpression
					105%
					2016
					Proteins bind IGF1/2, degraded during pregnancy, delay in sexual maturity
					86
				
			

				
					PAPP-A on high-fat diet
					105%
					2015
					Males chosen so no adverse developmental effect on fat depots
					87
				
			

				
					clk-1(-/-) with clk-1 transgene
					128%
					2014
					clk-1 functions in ubiquinone synthesis, but levels weren't very affected.
					88
				
			

				
					AgRP -/-
					110%
					2006
					Neuropeptide that is appetite stimulator, overexpression leads to hyperphagia and obesity.
					89
				
			

				
					Bone marrow transplantation
					106%
					2013
					Bone marrow transplantation from young to old mice was claimed to extend lifespan
					90
				
			

				
					Young blood injections
					94%
					2014
					Resulted in decreased lifespan
					91
				
			

				
					Nas(-/-) mice
					125%
					2011
					Hyposulfatemic NaS1 null mice (Nas1 -/-) had an increased lifespan compared to wildtype control.
					92
				
			

				
					Cyclophilin D (+/-)
					119%
					2017
					Decrease in maximum lifespan
					93
				
			

				
					PAPP-A in adults
					120%
					2017
					Tamoxifen-induced knockdown
					94
				
			

				
					Mtbp (+/-)
					120%
					2016
					Rotarod, open field, blood glucose, insulin, IGF-1 were the same.
					95
				
			
			
		
	