| 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 |