| 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 | — | — | — |
| 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 | — | — |
| Tert gene therapy | Mice treated with an adeno-assoicated virus vector expressing TERT at the age of one lived 24% longer on average and those treated at the age of two, by 13%. Maximum lifespan of the mice treated at 1 and 2 years was also extended by and 13% and 20%, respectively. AAV9-mTERT treated mice also had improved health, delayed onset of age-related diseases (like osteoporosis and insulin resistance) as well as improved readings in ageing indicators like neuromuscular coordination [22585399].
The gene therapy consists of a single injected via tail vein and achieved a transduction efficiency of 20-50%. Already 1 month after treatment, the treated mice at both age groups had longer telomeres and a decrease in the short telomeres in multiple tissues, while the controls exhibit an increase in short telomerase. In contrast to their control littermates at 3 and 8 months post-treatment the blood of most of the AAV9-treated mice at 1 year had no decrease or exhibit even a net increase in average telomere length and had also no increase or even a marked decrease in percentage of short telomeres with time. Thus, the therapy achieved in perhipheral blood leukocytes a prevention of telomere shortening. Treated mice had lower leves of fasting insulin, improved glucose tolerance and better homeostatic model assessment. Two years old treated mice had higher IGF1 levels. Treated mice at both ages had improved memory scores. AAV9-mTERT treatment increased cyclinD1 positive cells in various tissues. Upon AAV9-mTERT treatment levels of p16 decreased in most organs (with exception of heart). The metabolic and mitochondrial decline in 2 years old mice treated was not as apparent as in controls [22585399].
| Mouse | +13 to +24 | — | +13 to +20 |
| rps-27 RNAi | Knockdown of rps-27 by RNAi extends mean and maximum lifespan by 50 and 44%, respectively [19293945]. | Worm | +50 | — | +44 |
| old-2 overexpression | Overexpression of old-2 increases slightly, although statistically significant mean and maximum lifespan by 19 and 44% [9768365]. | Worm | +19 | — | +44 |
| old-1 overexpression | Overexpression of old-1 in transgenic animals increases mean and maximum lifespan by 40-100% (average 65%) and 97%, respectively. old-1 overexpression of increases stress resistance (to heat by 20% and ultraviolet irradiation by 33%) without altering development or fertility. Effects of old-1 on lifespan and stress resistance is under regulation of daf-16 [9768365]. | Worm | +40 to +100 | — | +97 |
| 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 | — | — |
GenAge
GenDR
