| SAG12 | senescence-associated protein 12 | Expression of SAG12 is specifically activated by developmentally controlled senescence pathways but not by stress- or hormone-controlled pathways [10579486; 10579487]. | — |
| arf-3 | ADP-Ribosylation Factor related 3 | RNA interference of arf-3 does not affect lifespan of wild-type but suppresses lifespan extension by isp-1 mutation [22829775]. | — |
| — | 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]. | — |
| H2S | Hydrogen Sulfide | Hydrogen sulfide (H2S) is a colorless, poisonousness, flammable gas with the characteristic foul odor of rotten eggs. A few breath of air containing high levels H2S can cause death, while lower long-term exposure can cause eye irritation, headache, and fatigue.
The human body produces small amounts of hydrogen sulfide and uses it as signaling molecule. It has a variety of physiological effects. For instance, it relaxes the vascular endothelium and smooth muscle cells, which is important to maintaining clean arteries as one ages. It is an important signaling molecule because of its significant effects on the cardiovascular and nervous systems.
Hydrogen sulfide appears to slow aging by inhibiting free-radical reactions via the activation of SIRT1 and probably through its Interactions with Klotho.
Klotho seems to be upregulated by hydrogen sulfide and extends lifespan via a number of different pathways, some of which promote production of endogenous antioxidants.
H2S produced in the kidneys has direct angiotension-converting enzyme (ACE) inhibiting activity. It is therefore an ACE inhibitor, just like certain drugs that mitigate high blood pressure.
Plasma hydrogen sulfide declines with age and is lower in spontaneously hypertensive rats. A lack of hydrogen peroxide is in general implicated in cardiovascular disease. Declining hydrogen sulfide levels also underline neurological health. Endogenous hydrogen sulfide is lower in animal model of Parkinson disease and depressed in the brains of patients with Alzheimer's disease. Hydrogen sulfide may also protective in animal models as well as humans against cancer [23297346]. | — |
| 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 |
| ZTA1 | Zeta-crystallin homolog, found in the cytoplasm and nucleus; has similarity to E. coli quinone oxidoreductase and to human zeta-crystallin, which has quinone oxidoreductase activity | Deletion of ZTA1 increases replicative lifespan by 15% in the alpha strain and decreased by 10% in the a strain [18340043]. Although ZTA1 was identified as a potential long-lived mutant strain in a bar-code screen, deletion of ZTA1 does not significantly affect chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| ACB1 | Acyl-CoA-Binding 1 | ACB1 deletion extends chronological lifespan under starvation/extreme DR. Similar heat-shock resistance and resistance to a very hight concentration of acetic acid (but not resistance to oxidative stress) was enhanced by the deletion of ACB1. Deletion of ACB1 in W303-1A and DBY746 genetic backgrounds on synthetic complete media causes severe growth defects and sightly shorter lifespan and also heat-sensitivity [20657825]. | Budding yeast |
| 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 |
| FAR3 | Factor ARrest 3 | Deletion of FAR3 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. | Budding yeast |
| FAR11 | Factor ARrest 3 | Deletion of FAR11 significantly reduces mean chronological lifespan under starvation/extreme DR relatively to wild-type [20657825]. | Budding yeast |
| PPG1 | Protein Phosphatase involved in Glycogen accumulation 1 | PPG1 deletion reduces significantly mean chronological lifespan under starvation/extreme DR [20657825]. | Budding yeast |
| 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 |
| ABP1 | Actin Binding Protein 1 | ABP1 deletion increases replicative lifespan by 30% in the alpha strain and decreases replicative lifespan by 20% in the a strain [18340043]. Deletion of ABP1 increases replicative lifespan by 20% in the alpha strain and decreases replicative lifespan by 20% in the a strain [19030232]. | Budding yeast |
| 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 |
| TPK2 | Takashi's Protein Kinase 2 | Deletion of TPK2 in a tpk1 and tpk3 double mutant background decreases PKA activity and extends replicative lifespan by approximately 25% in SGY446 strain [11000115]. | Budding yeast |
| YMR226C | — | Replicative lifespan of TMA29 mutants increases by 35% in the alpha strain and decreases by 10% in the a strain [18340043]. | Budding yeast |
| YDR124W | — | Deletion of YDR124W increases replicative lifespan by 30% in the alpha and decreases lifespan by 10% in a strain [19030232]. | Budding yeast |
| TAD1 | tRNA-specific Adenosine Deaminase 1 | Deletion of TAD1 does non-significantly increase the mean replicative lifespan by 14% [20550517]. | Budding yeast |
| FCY1 | FluoroCYtosine resistance 1 | Deletion of FCY1 does non-significantly decrease mean and maximum replicative lifespan by 4% and 8%, respectively [20550517]. | Budding yeast |
| SML1 | Suppressor of Mec1 Lethality 1 | Deletion of SML1 increases non-significantly mean replicative lifespan by 3% and non-significantly maximum lifespan by 16% [20550517]. | Budding yeast |
| IDP3 | Isocitrate Dehydrogenase, NADP-specific 3 | Deletion of IDP3 results in a replicative lifespan increase by 15% in the alpha strain and decrease by 20% in the a strain [18340043; 19030232]. | Budding yeast |
| INP54 | Phosphatidylinositol 4,5-bisphosphate 5-phosphatase with a role in secretion, localizes to the endoplasmic reticulum via the C-terminal tail; lacks the Sac1 domain and proline-rich region found in the other 3 INP proteins | Replicative lifespan increased by 15% in the alpha strain and decreased by 15% in the a strain | Budding yeast |
| CTA1 | CaTalase A 1 | CTA1 overexpression partially suppresses the shortened chronological lifespan by ISC1 mutation [21707788]. | Budding yeast |
| NMD4 | Nonsense-Mediated mRNA Decay 4 | Deletion of NMD4 increases replicative lifespan [16293764]. NMD4 deletion results in replicative lifespan increase by 25% in the alpha strain and decrease by 20% in a strain [19030232]. | Budding yeast |
