sptf-3 Overexpression | Overexpression of sptf-3 extends lifespan [18059442]. | Worm | — | — | — |
ectopic Trp53 overexpression | Mutant mice with activated Trp53 display enhanced resistance to spontaneous tumours and signs of premature ageing including reduced lifespan, osteoporosis, organ atrophy and a diminished stress tolerance [11780111]. | Mouse | — | — | — |
super-Trp53 | super-p53 mice generate by integrating a transgenic copy of a large genomic segment containing an intact and complete copy of p53 have an ehanced response to DNA damage, are significantly protected from cancer and had no indication of accelerated aging [12426394]. | Mouse | — | — | — |
super-Ink4a/Arf | super-Ink4a/Arf mice carrying a transgenic copy of a large genomic segment containing an intact and complete copy of the Cdkn2a (a.k.a. Ink4a/Arf) gene are significantly protected from cancer and had no indication of accelerated aging. Cells derived from super-Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation [15520276]. | Mouse | — | — | — |
super-Ink4a/Arf/p53 | super-Ink4a/Arf/p53 mice have a synergic protection against cancer and delayed aging [Workshop RoSyBa 2011]. | Mouse | — | — | — |
Tert overexpression | Mice genetically modified to express telomerase lived 40% longer and do not develop cancer. Overexpression of Tert in mice engineered to be cancer-resistant by means of ehanced expression of p53, p16 and p19ARF (Sp53/Sp16/SARF/TgTERT) decreased telomere shortening with age, delayed aging and increases mean and median longevity by 40% [19013273]. | Mouse | +40 | +40 | — |
K5-Tert overxpression | Overexpression of telomerase results in a high cancer incidence but also a modest mean (10%) and maximum lifespan extension accompanied by a lower incidence of some age-related degenerative diseases, in particular those related to kidney function and germline integrity [15688016]. | Mouse | +10 | — | — |
Pink1 overexpression | Overexpression of Pink1 and overexpression of Pink1 with alpha-synclein results in an increase in lifespan which is accompanied by an increase in healthspan (as measured by mobility) when driven by a dopaminergic cells targeting TH-Gla4 transgene [22653599]. | Fly | — | — | — |
cup-4 overexpression | cup-4 overexpession reduces oxidative stress resistance and shortens lifespan of wild-type under AL [19783783]. | Worm | — | — | — |
nlp-7 overexpression | nlp-7 overexpression reduces oxidative stress resistance and shortens lifespan of wild-type under AL [19783783]. | Worm | — | — | — |
Cisd2 overexpression | A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects [22661501]. | Mouse | — | — | — |
Replacement of Cebpa by Cebpb | Replacing the Cebpa gene by Cebpb increases mean lifespan by about 20% [15289464]. C/ebpalpha(beta/beta) animals consume more food but weight less than controls [10982846], and have a slightly elevated body temperature (0.3-0.5 degree Celsius) [15289464]. | Mouse | +20 | — | — |
Overexpression of Cat and Sod1 | Simultaneous overexpression of catalase and Sod1 results in a one-third (i.e. 30%) lifespan extension, a slower rate of mortality acceleration, and a delayed loss in physical performance, but neither has any effect on lifespan alone [8108730]. | — | +30 | — | — |
CIT2 overexpression | Overexpression of CIT2 has no effect on replicative lifespan [10224252]. | Yeast | — | — | — |
clk-1 overexpression | Overexpression of clk-1 shortens lifespan and is associated with increased mitochondrial activity [10202142]. | Worm | — | — | — |
daf-18 overexpression | Overexpression increases adult lifespan in individual tissues [16153634]. | Worm | — | — | — |
Down syndrom | Individuals with Down syndrome develop the neuropathological lesions of Alzheimer disease significantly earlier than those without [3158266] and have a shorter lifespan. Down syndrome is cuased by duplication of small regions of chromosome 21 [8197171]. The major features of Down syndrome are mental retardation, characteristic facial features, congenital malformations of the heart and gastrointestinal tract, thyroid disease, and an increased incidence of leukaemia [Epstein, 1989]. Neurons cultured in vivo form individuals with Down syndrome degenerate and exhibit apoptosis [8524410]. Down syndrome neurons also display increased generation of reactive oxygen species and treatment with antioxidants can prevent degeneration. | Human | — | — | — |
Ef1alpha48D overexpression | Overexpression of Ef1alpha48D (transformed with a P-element vector and under control of hsp70 regulatory sequences) results in lifespan extension by 18-41% [2508089]. | Fly | +18 to +41 | — | — |
Mt2 overexpression | Overexpression of Mt2 extends mean and maximum lifespan [15533947]. | Fly | — | — | — |
FPS1S overexpression | Plants overexpressing FPS1S exhibit a cell death/senescence-like phenotype and grw vigorously than wild-type [12000449]. In plants with increased FPS activity, the expression of senescence activated gene SAG12 is prematurely induced. | — | — | — | — |
Ghr knockout | Ghr knockouts (the so called Laron mice) are dwarfs with significantly extended lifespan by 40-50% [12933651]. Ghr-/- mice are significantly longer lived as Ghr+/+ or Ghr+/- mice (by 40-50%) in both females and males [10875265; 19370397]. 30% DR fails to affect overall survival, average or median long-lifespan of Growth hormone receptor knockout (GHRKO) mice and increased maximal lifespan only in females. Insulin sensitivity in GHRKO mutants is greater than in wild-type and is not further increased by DR [16682650]. Intermittent fasting also fails to extend the long lifespan of GHRKO mice [19747233].
Lifespan of mice with a deletion in the Ghr gene live almost 5 years [21123740]. In C57BL/6J this mutation increases life expectancy by 16 to 26% depending on gender [12933651] and in mice of mixed genetic background the increases amounted to 36-55% [9371826]. Serum levels of GH are elevated in mutant mice [9371826] and mutants are smaller than wild-type. IGF-1 and IGFBP-3 levels are also reduced in Ghr mutant mice [10875265]. The age-associated decline in memory retention is delayed in Ghr mutants [11336996]. | Mouse | +16 to +55 | — | — |
GLaz overexpression | Overexpression of GLaz results in increased resistance to hyperoxia (100% O2) and a 29% extension of mean lifespan under normoxia. Lifespan was also extended 30-60% under starvation [16581512]. | Fly | +29 | — | — |
hsp-16 overexpression | Overexpression of the hsp-16 loci enhances stress resistance and extends mean lifespan by 11% at 20 degree Celsius. Lifespan extension by hsp-16 overexpression requires daf-16 [12882326]. | Worm | +11 | — | — |
HSP104 overexpression | Overexpression of HSP104 driven by GAL promoter is insufficient to extend replicative lifespan [9851879]. Overproduction of HSP104 in wild-type cells has no effect on replicative life span, but suppresses the reduced lifespan of Sir2-deficient cells [17908928]. HSP104 overproduction is sufficient to induce thermotolerance [8643570]. | Yeast | — | — | — |
Hsp26 overexpression | Overexpression of Hsp26 (by the UAS/GAL4 system) increases stress resistance and extends the mean lifespan by 30% [15308776]. | Fly | +30 | — | — |