Koschei the immortal and anti-aging drugs

Blagosklonny, Mikhail V.

doi:10.1038/cddis.2014.520

Cited by 36 publications

(36 citation statements)

References 203 publications

(205 reference statements)

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“…hGFs undergo irreversible senescence upon continuous replication [ 20 ]. Rapamycin-treated hGFs almost doubled their days before senescence when compared to control cells ( Figure 1(b) ).…”

Section: Resultsmentioning

confidence: 99%

mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

Xia

Sun

Xie

et al. 2017

Oxidative Medicine and Cellular Longevity

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The aging periodontium may be vulnerable to periodontal pathogens and poor response to inflammation and susceptible to tumorigenesis. Human gingival fibroblasts (hGFs) through continuously replicative culture served as an in vitro surrogate for aging. To investigate the effects of the mechanistic target of rapamycin (mTOR) inhibition on the aging gingiva, we stimulated the high-passage hGFs with rapamycin (20 nmol/L) for 3 days and 30 days. The cellular and biological changes were examined by immunofluorescence, real-time PCR, ELISA, Western blotting, and flow cytometry. The data demonstrated that the inhibition of mTOR signaling led to fewer senescence-associated beta-galactosidase- (SA-β-Gal-) positive cells, delayed the onset of senescence, preserved the capability of proliferation, and lowered the expression levels of relevant senescence-associated markers, such as p16INK4a, p21CIP1a, interleukin-6 (IL-6), and IL-8. In addition, when infected by prominent periodontal pathogens, Porphyromonas gingivalis (ATCC 33277), rapamycin-pretreated groups decreased the expression of inflammatory cytokines (IL-6 and IL-8) compared with the control group. mTOR inhibition upregulated the gene expression of antioxidant components (Cat, Sod2, and Prdx3; P < 0.05) and consequently neutralized the excessive reactive oxygen species (ROS). In conclusion, our results indicated that mTOR inhibition might rejuvenate the aging gingiva to some extent and relieve inflammation through eliminating oxidative stress.

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“…hGFs undergo irreversible senescence upon continuous replication [ 20 ]. Rapamycin-treated hGFs almost doubled their days before senescence when compared to control cells ( Figure 1(b) ).…”

Section: Resultsmentioning

confidence: 99%

mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

Xia

Sun

Xie

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…With the changing medical treatments and with the changes in the living environment, the age of the population is increasing in all countries, posing novel challenges to the medical and social areas [ 15 - 27 ]. While the changes related to increased age implies significant problems for the society, relevant modifications needs to be clarified for the physical, biological and mental health.…”

Section: Discussionmentioning

confidence: 99%

Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients

Noce

Canale

Capria

et al. 2015

Aging

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Vascular calcifications are frequent in chronic renal disease and are associated to significant cardiovascular morbidity and mortality. The long term predictive value of coronary artery calcifications detected by multi-layer spiral computed tomography for major cardiovascular events was evaluated in non-diabetic Caucasian patients on maintenance hemodialysis free of clinical cardiovascular disease. Two-hundred and five patients on maintenance hemodialysis were enrolled into this observational, prospective cohort study. Patients underwent a single cardiac multi-layer spiral computed tomography. Calcium load was quantified and patients grouped according to the Agatston score: group 1 (Agatston score: 0), group 2 (Agatston score 1-400), group 3 (Agatston score 401-1000) and group 4 (Agatston score >1000). Follow-up was longer than seven years. Primary endpoint was death from a major cardiovascular event. Actuarial survival was calculated separately in the four groups with Kaplan-Meier method. Patients who died from causes other than cardiovascular disease and transplanted patients were censored. The “log rank” test was employed to compare survival curves. One-hundred two patients (49.7%) died for a major cardiovascular event during the follow-up period. Seven-year actuarial survival was more than 90% for groups 1 and 2, but failed to about 50% for group 3 and to <10% for group 4. Hence, Agatston score >400 predicts a significantly higher cardiovascular mortality compared with Agatston score <400 (p<0.0001); furthermore, serum Parathyroid hormone levels > 300 pg/l were associated to a lower survival (p < 0.05). Extended coronary artery calcifications detected by cardiac multi-layer spiral computed tomography, strongly predicted long term cardiovascular mortality in non-diabetic Caucasian patients on maintenance hemodialysis. Moreover, it was not related to conventional indices of atherosclerosis, but to other non-traditional risk factors, as serum Parathyroid hormone levels. A full cost-benefit analysis is however necessary to justify a widespread use of cardiac multi-layer spiral computed tomography in clinical practice.

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“…It is not the side effects in rodents, per se, but such warnings that have halted the use of rapamycin for life extension. Still, rapamycin and its analog, everolimus, have already been studied for the prevention and treatment of age-related diseases [52], potentially giving humans a chance to live longer and healthier lives in our lifetime. [See the forthcoming article "The fear of immortality: but it is more dangerous not to use anti-aging drugs than to use them"].…”

Section: Rapamycin-induced Pseudo-diabetesmentioning

confidence: 99%

The mystery of the ketogenic diet: benevolent pseudo-diabetes

Blagosklonny

2019

Cell Cycle

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Designed a century ago to treat epilepsy, the ketogenic diet (KD) is also effective against obesity and diabetes. Paradoxically, some studies in rodents have found that the KD seemingly causes diabetes, contradicting solid clinical data in humans. This paradox can be resolved by applying the concept of starvation pseudo-diabetes, which was discovered in starved animals almost two centuries ago, and has also been observed in some rapamycin-treated rodents. Intriguingly, use of the KD and rapamycin is indicated for a similar spectrum of diseases, including Alzheimer’s disease and cancer. Even more intriguingly, benevolent (starvation) pseudo-diabetes may counteract type 2 diabetes or its complications.

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Koschei the immortal and anti-aging drugs

Cited by 36 publications

References 203 publications

mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress

Coronary artery calcifications predict long term cardiovascular events in non diabetic Caucasian hemodialysis patients

The mystery of the ketogenic diet: benevolent pseudo-diabetes

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