| Sirt1 | sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae) | Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any parameter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted [22560220]. Sirt1 overexpression mimicks the effect on reservatrol on mitochondrial function, but failed to extend lifespan [22560220].
SIRT1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in SIRT1 knock-out MEFs [16054100].
Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035].
Sirt1 is required for high-magnitude circadian transcription of several core clock genes. It deacetylates Per2, Arntl and histones of clock-controlled genes [18662546].
SIRT1 directly [21187328] and indirectly [20450879] prevents telomere shortening. | House mouse |
| ARO7 | AROmatic amino acid requiring 7 | Under starvation/extreme DR deletion of ARO7 increases mean chronological lifespan and confers higher resistance to heat-shock, but made cell more sensitive to acetic acid and leads to growth defects. In W303-1A background ARO7 deletion causes an even more severe growth defect and mutants are short-lived [20657825]. | Budding yeast |
| VPS27 | — | Under starvation conditions VPS27 deletion mutants have a dramatically reduced lifespan [20953148]. | Budding yeast |
| VPS25 | — | Under starvation conditions VPS25 deletion mutations have dramatically reduced lifespan [20953148]. | Budding yeast |
| unc-51 | UNCoordinated-51 | unc-51(e369) mutation reduces mean but extends maximum lifespan. unc-51(e369) mutation reduces lifespan of eat-2(ad1116) mutants to that of wild-type [18219227]. | Nematode |
| UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCHL1 is assoicated with Parkinson's disease [9774100]. UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts [11084366]. Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. | Human |
| SST | Somastatin | Two with age-related differential methylation markers lay within Somastatin (SST) [23177740] which declines with age and is linked to Alzheimer's disease [15778722]. | Human |
| TSHR | thyroid stimulating hormone receptor | Two single nucleotide in the TSHR were associated with increased TSH in both centenarians and their offspring [19837933].TSHR was found to be associated with longevity [19837933]. TSHR was not found to be associated with longevity [19837933]. | Human |
| NAC | N-acetyl cysteine | Treatment with 10 mM of NAC has no effect on the lifespan of wild-type, but fully abolishes the increased longevity of nuo-6 and severly limits that of isp-1. At high concentration (> 10-15 nM) NAC can be become deleteroius even on the wild-type [21151885]. | Nematode |
| Vitamin C | — | Treatment with 1 mM vitamin C has no effect on lifespan of wild-type, but significantly shortens the lifespan of both isp-1 and muo-6 mutants [21151885].
Supplementation with vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants, which both exhibit premature aging [23075628]. | Nematode |
| GH1 | Growth hormone 1 | Transgenic mice overexpressing bovine GH1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels [14583653]. | Cattle |
| EXO1 | exonuclease 1 | The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. | Human |
| SOD1 | SuperOxide Dismutase 1 | The overexpression of Sods, mitochondrial Sod2 and cytosolic CuZnSod (Sod1), in combination delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends chronological lifespan by 30% [12586694]. Deletion of SOD1 decreases replicative lifespan by 40% [17460215]. Overexpression of SOD1 with CCS1 levuates the level of Cn, Zn-Sod activity and increased chronological lifespan. However overexpression of SOD1 without high cooper or simultonous overexpression of CCS1 shortened both chronological and replicative lifespan [15659212]. Overexpression of SOD1 has no effect on replicative lifespan [10224252]. Deletion of SOD1 shortens replicative lifespan by approximately 40%. The magnitude of the decrease in lifespan does not appear to dependent on oxygen concentration in the atmosphere [12020810]. Deletion of SOD1 shortens replicative lifespan [10547026]. Deletion of SOD1 shortens replicative as well as chronological lifespan [10222047].
Cells with a deletion of SOD1 exhibit a profound defect in entry into and survival during stationary phase (i.e. chronological lifespan) in the W303-B strain [8647826; 10222047], which is partially suppressed by expression of human Bcl-2 [9199172].
Hypersensitivity to oxygene and significantly decreased replicative lifespan of SOD1 deletion can be ameliorated by exogenous ascorbate. If acorbate's negative effects of auto-oxidation are prevented by exchange of medium, ascorbate prolongs mean and maximum replicative lifespan in the atmosphere of air and pure oxygene [15621721].
SOD1 deletion causes sensitivity to hyperoxia as well as methionine and lysine auxotrohies [9199172].
| Budding yeast |
| — | Germline | Sterilization prolongs lifespan, in species from insect to humans.
In hermaphrodite C. elegans, removing sperm and egg-producing cells extends lifespan by 50%. Removing those cells triggers a reaction in the surrounding tissue. The signal is send out in the form of a steroid hormone, that turns on a molecular switch, which switches them into a kind of survival mode. Specifically, remaining gonadal cells trigger production of a steroid hormone dafachronic acid. Dafachronic acid activates miRNAs, which work as tiny molecular switch causing changes in gene expression that promote longevity. The same steroid hormone-miRNA switch is part of the developmental clock. The loss of the germ cells ultimately causes the worm to use developmental timers to put in motion a lifespan-prolonging programme [23239738]. | — |
| KLF14 | Kruppel-like factor 14 | Six aging differentially methylated markers lay within KLF14 [23177740]. | Human |
| sgg | shaggy | Several insertions of P-based vectors in the structural part of sgg are associated with alterations of male and female lifespan [22661237]. | Fruit fly |
| RTG2 | ReTroGrade regulation 2 | RTG2 is required for replicative lifespan extension associated with the retrograde response, a pathway that signals the functional status of mitochondria to the nucleus to regulate the expression of several genes [11024000]. RTG2 is not required for replicative lifespan extension by DR [11024000].
RTG2 null mutants are not petite [8422683], but display various nutrient auxotrphies and alterations of carbohydrate metabolism [7727418]. | Budding yeast |
| cul-1 | CULlin 1 | RNAi of cul-1 decreases lifespan of daf-2 mutant, but not of wild-type or glp-1 mutant. The CUL-1 complex functions in postmitotic, adult somatic tissues of insulin/insulin-like growth factor-1-signaling mutants to enhance longevity. It may act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO [17392428]. | Nematode |
| kri-1 | human KRIT 1 (Krev interaction trapped/cerebral cavernous malformation 1) homolog | RNA interference suppresses glp-1 life-extension but does not shorten lifespan of wildtype strains. kri-1(ok1251) mutation does not shorten the lifespan significantly [22560223]. | Nematode |
| Y46G5A.6 | phi-3 | RNA interference of Y46G5A.6 in adulthood shortens the extends lifespan of daf-2(mu150) mutants. Only a negligible or small reduction in the lifespan of wild-type worms occurs by knockdown of Y46G5A.6 [17392428]. | Nematode |
| tbc-7 | TBC (Tre-2/Bub2/Cdc16) domain family | RNA interference of tbc-7 decreased median lifespan by 28% in daf-2 mutants [18006689]. | Nematode |
| sbds-1 | Shwachman-Bodian-Diamond Syndrome protein homolog 1 | RNA interference of sbds-1 decreases median lifespan by 24% in daf-2 mutants [18006689]. RNAi knockdown of sbds-1 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. SBDS-1 are elevated in eat-2 mutants. Increased content of SBDS-1 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
| mdt-26 | MeDiaTor 26 | RNA interference of mdt-26 decreases the median lifespan 42% in daf-2 long-lived mutants [18006689]. | Nematode |
| cku-70 | Caenorhabditis KU 70 | RNA interference of cku-70 further increases the lifespan of daf-2 mutants. Lifespan of daf-16 mutants is slightly decreased by cku-70 RNAi [16099946]. | Nematode |
| C29F9.1 | — | RNA interference of C29F9.1 decreases median lifespan by 35% in daf-2 mutants [18006689]. | Nematode |
