BHB | β-hydroxybutyrate | β-hydroxybutyrate (βOHB), ketone body is produced during a prolonged low-caloric or ketonic diet.
Low concentrations of βOHB helps protect cells from "oxidative stress". dietary restriction (DR) spurs βOHB production. βOHB is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Exogenous βOHB administration, fasting or DR increases global histone acetylation in mouse tissues. HDAC inhibition by βOHB is correlated with global changes in transcription, including oxidative stress factors Foxo3a and Mt2. Cells treated with βOHB have increased histone acetylation at Foxo3a and Mt2 promoters. Both Foxo3a and Mt2 are activated by selective depletion of HDAC1 and HDAC2. normally keeps a pair of genes, namely Foxo3a and Mt2 switched off [http://www.biocompare.com/Life-Science-News/126847-Gladstone-Scientists-Discover-Novel-Mechanism-By-Which-Calorie-Restriction-Influences-Longevity/; http://www.sciencemag.org/content/early/2012/12/05/science.1227166]. | — |
zyg-11 | ZYGote defective: embryonic lethal | zyg-11 RNAi in the adulthood extends the lifespan [New longevity regulators]. | Nematode |
ZWINT | ZW10 interactor | ZWINT was found to be associated with longevity [22279548]. | Human |
ZNF331 | zinc finger protein 331 | ZNF331 was found to be associated with longevity [21782286]. | Human |
ZC395.10 | Zinc finger Transcription Factor family | ZC395.10 RNAi in the adulthood extends the lifespan [New longevity regulators]. | Nematode |
ZBTB20 | zinc finger and BTB domain containing 20 | ZBTB20 was found to be associated with longevity [22279548]. | Human |
YPT7 | Yeast Protein Two 7 | YPT7 deletion decreases replicative lifespan by 15% in the alpha strain [18340043]. Deletion of YPT7 cancels out replicative lifespan extension of 0.5% glucose restriction and results under DR also into a shorter replicative lifespan than under AL [18690010]. | Budding yeast |
YHC3 | Yeast Homolog of human Cln3 | YHC3 deletion decreases 10-20% shortened lifespan [16435200]. | Budding yeast |
YGL235W | — | YGL235W increases replicative lifespan by 20% in the alpha strain [19030232]. | Budding yeast |
YDL180W | — | YDL180W deletion impairs DR-mediated replicative lifespan extension, but does not change lifespan on AL significantly [22912585]. | Budding yeast |
yata | — | yata mutation shortens the maximum lifespan by 68% and results in progressive deterioration of the nervous tissues and aberrant accumulation of Sec23 [19209226]. | Fruit fly |
Yaf2 | YY1 associated factor 2 | Yaf2 is transcriptional upregulated in the cerebral cortex at the age 28 months under different longevity conditions such as under dietary restriction (DR) as well as in feeding switch regimens that result in extended lifespan, like early age switch to DR as well as the reverse switch under the influence of the DR-mimetic α-lipoic acid (i.e. DR switched to ad libitum+ lipoic acid) [Shona et al. 2013]. | Norway rat |
Y56A3A.9 | — | Y56A3A.9 RNA interference extends lifespan. | Nematode |
Y41E3.11 | human FANCD2 (Fanconi's anemia defect) ortholog | Y41E3.11 RNAi in the adulthood extends the lifespan [New longevity regulators]. | Nematode |
xrn-1 | XRN (mouse/S. cerevisiae) ribonuclease related | xrn-1 RNAi in the adulthood extends the lifespan [New longevity regulators]. | Nematode |
XRCC5 | X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining) | XRCC5 was found to be associated with longevity [22406557; 16518718]. | Human |
Xrcc6 | X-ray repair complementing defective repair in Chinese hamster cells 6 | XRCC5 and XRCC6 double knockout mice show decreased lifespan and signs of premature ageing without increase cancer incidence. | House mouse |
XRCC4 | X-ray repair complementing defective repair in Chinese hamster cells 4 | XRCC4 was found to be associated with longevity [16518718]. | Human |
XRCC3 | X-ray repair complementing defective repair in Chinese hamster cells 3 | XRCC3 was found to be associated with longevity [16518718]. | Human |
XRCC1 | X-ray repair complementing defective repair in Chinese hamster cells 1 | XRCC1 was found to be associated with longevity [16518718]. | Human |
XKR6 | XK, Kell blood group complex subunit-related family, member 6 | XKR6 was found to be associated with longevity [22279548]. | Human |
XDH | xanthine dehydrogenase | XDH was found to be associated with longevity [22406557; 22279548]. | Human |
WWOX | WW domain containing oxidoreductase | WWOX was found to be associated with longevity [22279548]. WWOX was found to be associated with longevity [24244950]. | Human |
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 |
WDR72 | WD repeat domain 72 | WDR72 was found to be associated with longevity [22279548]. | Human |