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]. | — |
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 |
unc-52 | UNCoordinated 52 | RNA interference of unc-52 in adulthood extends mean lifespan by 11% [17411345]. RNAi knockdown of unc-52 starting at hatching or only during the adulthood significantly decreases lifespan of eat-2 without affecting wild-type lifespan. UNC-52 levels are elevated in eat-2 mutants. Increased content of UNC-52 is, at least partially, required for lifespan-extension by DR [22810224]. | Nematode |
U4 | U4 spliceosomal RNA | U4 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 |
Tmem218 | Transmembrane protein 218 | Tmem218 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 |
Tceb2 | Transcription elongation factor B polypeptide 2 | Tceb2 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 |
Thrsp | Thyroid hormone-inducible hepatic protein | Thrsp 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 |
Txnrd1 | Thioredoxin reductase 1, cytoplasmic | Txnrd1 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 |
sodh-1 | SOrbitol DeHydrogenase family 1 | RNA interference of sodh-1 does not affect the lifespan of eat-2 mutants, although SODH-1 is elevated in eat-2 mutants [22810224]. | 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 |
Sars | Seryl-tRNA synthetase, cytoplasmic | Sars 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 |
Rogdi | rogdi homolog (Drosophila) | Rogdi 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 |
Rpusd1 | RNA pseudouridylate synthase domain-containing protein 1 | Rpusd1 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 |
Resp18 | Regulated endocrine-specific protein 18 | Resp18 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 |
Rala | Ras-related protein Ral-A | Rala 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 |
Rab3b | RAB3B, member RAS oncogene family | Rab3b 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 |
PNC1 | Pyrazinamidase/NiCotinamidase 1 | Cells with 5 copies of PNC1 have a 70% longer replicative lifespan which is cancelled out by SIR2 deletion. PNC1 is upregulated under glucose DR [12736687]. Pnc1 reduces cellular nicotinamide levels, a product and noncompetitive inhibitor of Sir2 deacetylation reaction. Overexpression of PNC1 suppresses the effect of exogenously added nicotinamide on Sir2-dependent silencing at HM loci, telomeres and rDNA loci [12736687; 14729974]. Pnc1 catalyses the breakdown of nicotinamide to nicotinate and ammonia [12736687]. Deletion of PNC1 shortens replicative lifespan approximately by 10% [12736687] and largely prevents replicative lifespan extension of 0.5% glucose restriction. 0.5% glucose restriction slightly extends median replicative lifespan (by 10 - 15%) but not maximum replicative lifespan in pnc1Delta [14724176]. PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, lifespan, and Hst1-mediated transcriptional repression [14729974]. Increased expression of PNC1 is both necessary and sufficient for replicative lifespan extension by DR and low-intensity stress. Under non-stressing conditions (2% glucose, 30 degree Celsius), a strain with additional copies of PNC1 (5XPNC1) has 70% longer replicative lifespan than the wild-type and some cells live for more than 70 divisions. Neither DR nor heat stress further increase the lifespan of the 5XPNC1 strain [12736687]. PNC1 deletion decreases chronological lifespan [17110466]. | Budding yeast |
Pdcd5 | programmed cell death protein 5 | Pdcd5 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 |
PGA3 | Processing of Gas1p and ALP | Low glucose condition induces expression and activity of plasma membrane NADH coenzyme Q reductase (PGA3). Overexpression of PGA3 extends replicative and chronological lifespan by 20-30% [19239415]. | Budding yeast |
LOC100361934 | NADH dehydrogenase (ubiquinone) 1 beta subcomplex 4 | LOC100361934 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 |
Mir98 | microRNA mir-98 | miR-98-3p is the only miRNA significantly differentially expressed (upregulated) under DR and LA (lipoic acid; a DR-mimetic) treatment. Across mouse, rat and human predicted targets of miR-98-3p include the glutamate receptors, calcium transporters, histones and histone acetyltransferase/deacetylases.
miR-89-3p is expressed at a low level and is highly conserved in rat, mouse, human and anplis lizard. Mir-98 precursor is located on the X-chromosome. In the rat, mouse and human genome it overlaps an E3 ubiquitin ligase HUWE which is involved in regulation of apoptosis, regulation of neural differentiation and proliferation, DNA damage repair [Shona et al. 2013].
miR-98 expression is significantly decreased in the adventitia and endomembrane ath different degrees in Goto-Kakizaki rat, a model of type 2 diabetes. miR-98 targets TRB2 which is increased in expression in this model of type 2 diabetes. TRB2 phosphorylates Akt [22012613].
The mouse ortholog of Mir98 may by associated with the germline [16766679]. | Norway rat |
Lamc1 | laminin, gamma 1 | Lamc1 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 |
HES1 | Homologous to kES1 1 | Deletion of HES1 (alias OSH5) extends replicative lifespan and is non-additive with moderate DR. Elevation of OSH5 levels by an ERG6 promoter reduces mean, median and maximum replicative lifespan by 25, 18 and 29%. HES1 is required for the longevity effect of DR, Perg6-OSH6, Perg6-ERG2 and Perg6-OSH7 (genetic mimetics of DR). Hes1 is upregulated in response to sterol down-regulation including DR. Deletion of OSH5 delays different steps of endocytosis, a sterol-requireing process [Xia et al., unpublished].
Perg6-OSH6 osh5 double mutant have a lifespan significantly shorter than that of Perg6-OSH6 [Xia et al. upublished]. | Budding yeast |
gpa2 | Guanine nucleotide-binding protein alpha-2 subunit | gpa2 (alias git8) encodes the alpha subunit of a heterotrimeric G protein, which acts downstream of Git3. Git8 activity accelerates aging and inhibits the lifespan-extending effect of DR. Constitutive active mutation of gpa2 decreases chronological lifespan under AL (2% glucose) and almost completely cancels out the lifespan extending effect of DR (0.2% glucose) [19266076]. | Fission yeast |
Gadd45gip1 | Growth arrest and DNA damage-inducible proteins-interacting protein 1 | Gadd45gip1 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 |