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Knowledge Knight, Fact Fight, High IQ Insight
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First (short summary)
Progonadal Role of the Pineal in the Djungarian Hamster (Phodopus sungorus sungorus): Mediation by Melatonin* | Endocrinology | Oxford Academic
Short day exposure (10 hours light) regressed testicular development but not in pinealectomized hamsters. In mice with pineal glands, testes spontaneously began to grow, but transfer to long days induced a 15-fold increase in testes weight within 6 weeks and increased FSH over 4-fold. 4 hour and 6 hour daily melatonin infusions increased FSH and induced reproductive development to the same degree whether the release rate was 0.83 ng/hr or 83 ng/hr. Whereas, 8 hour or 12 hour infusions did not induce reproductive effects in the short day exposed mice.
Melatonin receptor density is regulated in rat pars tuberalis and suprachiasmatic nuclei by melatonin itself
Specific binding of melatonin (with an iodine-125 isotope attached) to its receptors in the pars tuberalis was increased by 3 days of constant light or pinealectomy, showing a sensitization effect to factors that decreased melatonin. A single injection of 50 micrograms melatonin reversed this sensitization effect. A similar result was found in the suprachiasmatic nuclei, except that in this case the melatonin injection only partly reversed the sensitization.
Melatonin Receptors in the Lamb Pars tuberalis/Median Eminence throughout the Day | Neuroendocrinology | Karger Publishers
Based on patterns of assays of lambs slaughtered, melatonin receptor density increased in the pars tuberalis/median eminence increased from midday to dusk, and then decreased throughout the night reaching densities lower than midday during midnight and dawn.
Second (detailed analysis)
Aspirin reduces endothelial cell senescence - ScienceDirect
100 micromolars of aspirin reduced beta-galactosidase positive-cells at cummulative population doubling 40 (CPD40), and the nitric oxide inhibitor L-NAME prevented this, but its enantiomer D-NAME did not prevent aspirin’s decrease in beta-galactosidase. In contrast, 100 micromolars of ibuprofen or acetaminophen increased beta-galactosidase positive-cells at cummulative population doubling 40.
ROS was increased from CPD20 to CPD40, and aspirin inhibited this increase whilst L-NAME prevented aspirin’s inhibition and D-NAME did not.
Nitric oxide decreased from CPD20 to CPD40. Aspirin increased nitric oxide (NO) concentrations at both intervals, and again L-NAME prevented aspirin’s increase in NO and D-NAME did not.
Asymmetric dimethylarginine (AMDA) was increased from CPD20 to CPD40, and aspirin inhibited this increase whilst L-NAME prevented aspirin’s inhibition and D-NAME did not. Nitric oxide decreased from CPD20 to CPD40.
Dimethylarginine dimethylaminohydrolase decreased from CPD20 to CPD40. Aspirin increased DDAH concentrations at both intervals, and again L-NAME prevented aspirin’s increase in DDAH and D-NAME did not.
This data suggests that aspirin increases DDAH to lower AMDA, which results in increased NO, since AMDA interferes with NO production. The increased NO from aspirin reduces ROS increase associated with replicative passage, thereby decreasing replicative senescence.
Third (explanation with quotations)
Gut microbiota mediate the FGF21 adaptive stress response to chronic dietary protein-restriction in mice | Nature Communications
18 vs 10 percent protein by weight. Cellulose (5 and 15 percent) reduced the FGF21 increase in response to PR, whilst inulin (5 and 15 percent) increased the FGF21 response to PR. Neither had significant effect on FGF21 in non-PR mice. “We found that Sutterella was the only genus whose relative abundance positively correlated with plasma FGF21 con-centrations while Parabacteroides, Lactococcus, Blautia, Strep-tococcus, and Anaerofustis were negatively correlated with FGF21” Parabacteroides, Lactococcus, Blautia, Streptococcus were enriched by 15% cellulose whereas Sutterella was enriched by 15% inulin.
Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening - Liao - 2010 - Aging Cell - Wiley Online Library
40% restriction (60% of ad libitum) was started at 2-5 months of age in 41 ILSXISS recombinant inbred mouse strains, and it was adjusted for each strain. Mean lifespan of strains under AL ranged from 504 to 1152 days in males and from 407 to 1208 days in females. Mean lifespan of strains under CR ranged from 217 to 1215 days in males and 113 to 1225 days in females.
“Heritability of lifespan under AL feeding was 28% (males) and 36% (females) and under DR was 55% (males) and 53% (females).”
Mean lifespan of 5% of the strains for males and 21% of the strains for females were extended with CR, and mean lifespans of males and females were correlated under CR and AL conditions. Maximum lifespan was correlated with mean lifespan under both conditions, and exclusion of early deaths (before 1 year) did not affect frequency of lifespan shortening. Thus, early deaths were not the reason for CR-induced lifespan shortening.
There was no correlation between absolute food intake and lifespan of CR mice, and there was no correlation between female fertility and lifespan of CR mice.
Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome | Journal of Cell Biology | Rockefeller University Press
Resveratrol but not spermidine requires SIRT1 activity to induce autophagy.
Both deacetylate ATG5 and LC3 to induce autophagy.
Spermidine doesn’t require SIRT2 to extend lifespan: ”Consistently, spermidine prolonged the lifespan of WT and sir-2.1–deficient worms by 18 and 13%, respectively.”
Spermidine putatively is an acetylase inhibitor, whereas resveratrol putatively activates SIRT1, which is a deacetylator. But it appears there is compensatory action regarding acetylation: “Based on this consideration, it appears paradoxical that neither of these two agents was able to provoke a general deacetylation state and that both of them actually stimulated a similar shift in the acetylation pattern, in which hundreds of proteins were deacetylated (more in the cytosol than in the nucleus), whereas several others were acetylated (more in the nucleus than in the cytosol).”
Progonadal Role of the Pineal in the Djungarian Hamster (Phodopus sungorus sungorus): Mediation by Melatonin* | Endocrinology | Oxford Academic
Short day exposure (10 hours light) regressed testicular development but not in pinealectomized hamsters. In mice with pineal glands, testes spontaneously began to grow, but transfer to long days induced a 15-fold increase in testes weight within 6 weeks and increased FSH over 4-fold. 4 hour and 6 hour daily melatonin infusions increased FSH and induced reproductive development to the same degree whether the release rate was 0.83 ng/hr or 83 ng/hr. Whereas, 8 hour or 12 hour infusions did not induce reproductive effects in the short day exposed mice.
Melatonin receptor density is regulated in rat pars tuberalis and suprachiasmatic nuclei by melatonin itself
Specific binding of melatonin (with an iodine-125 isotope attached) to its receptors in the pars tuberalis was increased by 3 days of constant light or pinealectomy, showing a sensitization effect to factors that decreased melatonin. A single injection of 50 micrograms melatonin reversed this sensitization effect. A similar result was found in the suprachiasmatic nuclei, except that in this case the melatonin injection only partly reversed the sensitization.
Melatonin Receptors in the Lamb Pars tuberalis/Median Eminence throughout the Day | Neuroendocrinology | Karger Publishers
Based on patterns of assays of lambs slaughtered, melatonin receptor density increased in the pars tuberalis/median eminence increased from midday to dusk, and then decreased throughout the night reaching densities lower than midday during midnight and dawn.
Second (detailed analysis)
Aspirin reduces endothelial cell senescence - ScienceDirect
100 micromolars of aspirin reduced beta-galactosidase positive-cells at cummulative population doubling 40 (CPD40), and the nitric oxide inhibitor L-NAME prevented this, but its enantiomer D-NAME did not prevent aspirin’s decrease in beta-galactosidase. In contrast, 100 micromolars of ibuprofen or acetaminophen increased beta-galactosidase positive-cells at cummulative population doubling 40.
ROS was increased from CPD20 to CPD40, and aspirin inhibited this increase whilst L-NAME prevented aspirin’s inhibition and D-NAME did not.
Nitric oxide decreased from CPD20 to CPD40. Aspirin increased nitric oxide (NO) concentrations at both intervals, and again L-NAME prevented aspirin’s increase in NO and D-NAME did not.
Asymmetric dimethylarginine (AMDA) was increased from CPD20 to CPD40, and aspirin inhibited this increase whilst L-NAME prevented aspirin’s inhibition and D-NAME did not. Nitric oxide decreased from CPD20 to CPD40.
Dimethylarginine dimethylaminohydrolase decreased from CPD20 to CPD40. Aspirin increased DDAH concentrations at both intervals, and again L-NAME prevented aspirin’s increase in DDAH and D-NAME did not.
This data suggests that aspirin increases DDAH to lower AMDA, which results in increased NO, since AMDA interferes with NO production. The increased NO from aspirin reduces ROS increase associated with replicative passage, thereby decreasing replicative senescence.
Third (explanation with quotations)
Gut microbiota mediate the FGF21 adaptive stress response to chronic dietary protein-restriction in mice | Nature Communications
18 vs 10 percent protein by weight. Cellulose (5 and 15 percent) reduced the FGF21 increase in response to PR, whilst inulin (5 and 15 percent) increased the FGF21 response to PR. Neither had significant effect on FGF21 in non-PR mice. “We found that Sutterella was the only genus whose relative abundance positively correlated with plasma FGF21 con-centrations while Parabacteroides, Lactococcus, Blautia, Strep-tococcus, and Anaerofustis were negatively correlated with FGF21” Parabacteroides, Lactococcus, Blautia, Streptococcus were enriched by 15% cellulose whereas Sutterella was enriched by 15% inulin.
Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening - Liao - 2010 - Aging Cell - Wiley Online Library
40% restriction (60% of ad libitum) was started at 2-5 months of age in 41 ILSXISS recombinant inbred mouse strains, and it was adjusted for each strain. Mean lifespan of strains under AL ranged from 504 to 1152 days in males and from 407 to 1208 days in females. Mean lifespan of strains under CR ranged from 217 to 1215 days in males and 113 to 1225 days in females.
“Heritability of lifespan under AL feeding was 28% (males) and 36% (females) and under DR was 55% (males) and 53% (females).”
Mean lifespan of 5% of the strains for males and 21% of the strains for females were extended with CR, and mean lifespans of males and females were correlated under CR and AL conditions. Maximum lifespan was correlated with mean lifespan under both conditions, and exclusion of early deaths (before 1 year) did not affect frequency of lifespan shortening. Thus, early deaths were not the reason for CR-induced lifespan shortening.
There was no correlation between absolute food intake and lifespan of CR mice, and there was no correlation between female fertility and lifespan of CR mice.
Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome | Journal of Cell Biology | Rockefeller University Press
Resveratrol but not spermidine requires SIRT1 activity to induce autophagy.
Both deacetylate ATG5 and LC3 to induce autophagy.
Spermidine doesn’t require SIRT2 to extend lifespan: ”Consistently, spermidine prolonged the lifespan of WT and sir-2.1–deficient worms by 18 and 13%, respectively.”
Spermidine putatively is an acetylase inhibitor, whereas resveratrol putatively activates SIRT1, which is a deacetylator. But it appears there is compensatory action regarding acetylation: “Based on this consideration, it appears paradoxical that neither of these two agents was able to provoke a general deacetylation state and that both of them actually stimulated a similar shift in the acetylation pattern, in which hundreds of proteins were deacetylated (more in the cytosol than in the nucleus), whereas several others were acetylated (more in the nucleus than in the cytosol).”
