Volume 5, Issue 8

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                TY  - JOUR
                AU  - Blagosklonny, Mikhail V. 
                TI  - Rapamycin extends life- and health span because it slows aging
                JO  - 
                JA  - 
                VL  - 5
                IS  - 8
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100591
                DO  - 10.18632/aging.100591
                SP  - 592
                EP  - 598
                PY  - 
                AB  - Making headlines, a thought-provocative paper by Neff, Ehninger and coworkers claims that rapamycin extends life span but has limited effects on aging. How is that possibly possible? And what is aging if not an increase of the probability of death with age. I discuss that the JCI paper actually shows that rapamycin slows aging and also extends lifespan regardless of its direct anti-cancer activities. Aging is, in part, MTOR-driven: a purposeless continuation of developmental growth. Rapamycin affects the same processes in young and old animals: young animals' traits and phenotypes, which continuations become hyperfunctional, harmful and lethal later in life.
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Serum from humans on long-term calorie restriction enhances stress resistance in cell culture

Daniela Omodei, Danilo Licastro, Francesco Salvatore, Seth D. Crosby, Luigi Fontana,

https://doi.org/10.18632/aging.100584 pp 599—606

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Omodei D, Licastro D, Salvatore F, Crosby SD, Fontana L, . Serum from humans on long-term calorie restriction enhances stress resistance in cell culture. . 5:599-606. https://doi.org/10.18632/aging.100584

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                TY  - JOUR
                AU  - Omodei, Daniela 
                AU  - Licastro, Danilo 
                AU  - Salvatore, Francesco 
                AU  - Crosby, Seth D. 
                AU  - Fontana, Luigi 
                TI  - Serum from humans on long-term calorie restriction enhances stress resistance in cell culture
                JO  - 
                JA  - 
                VL  - 5
                IS  - 8
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100584
                DO  - 10.18632/aging.100584
                SP  - 599
                EP  - 606
                PY  - 
                AB  - Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well.
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Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production

Shubhankar Suman, Olga C. Rodriguez, Thomas A. Winters, Albert J. Fornace Jr, Chris Albanese, Kamal Datta,

https://doi.org/10.18632/aging.100587 pp 607—622

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Suman S, Rodriguez OC, Winters TA, Fornace AJ, Albanese C, Datta K, . Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production. . 5:607-622. https://doi.org/10.18632/aging.100587

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                TY  - JOUR
                AU  - Suman, Shubhankar 
                AU  - Rodriguez, Olga C. 
                AU  - Winters, Thomas A. 
                AU  - Fornace, Albert J. 
                AU  - Albanese, Chris 
                AU  - Datta, Kamal 
                TI  - Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production
                JO  - 
                JA  - 
                VL  - 5
                IS  - 8
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100587
                DO  - 10.18632/aging.100587
                SP  - 607
                EP  - 622
                PY  - 
                AB  - Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation.
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Berberine suppresses gero-conversion from cell cycle arrest to senescence

Hong Zhao, H Dorota Halicka, Jiangwei Li, Zbigniew Darzynkiewicz,

https://doi.org/10.18632/aging.100593 pp 623—636

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Zhao H, Halicka HD, Li J, Darzynkiewicz Z, . Berberine suppresses gero-conversion from cell cycle arrest to senescence. . 5:623-636. https://doi.org/10.18632/aging.100593

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                TY  - JOUR
                AU  - Zhao, Hong 
                AU  - Halicka, H Dorota 
                AU  - Li, Jiangwei 
                AU  - Darzynkiewicz, Zbigniew 
                TI  - Berberine suppresses gero-conversion from cell cycle arrest to senescence
                JO  - 
                JA  - 
                VL  - 5
                IS  - 8
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100593
                DO  - 10.18632/aging.100593
                SP  - 623
                EP  - 636
                PY  - 
                AB  - Berberine (BRB), a natural alkaloid, has a long history of medicinal use in both Ayurvedic and old Chinese medicine. Recently, available as a dietary supplement, Berberine is reported to have application in treatment of variety diseases. Previously we observed that BRB inhibited mTOR/S6 signaling concurrently with reduction of the level of endogenous oxidants and constitutive DNA damage response. We currently tested whether Berberine can affect premature, stress-induced cellular senescence caused by mitoxantrone. The depth of senescence was quantitatively measured by morphometric parameters, senescence-associated β-galactosidase, induction of p21WAF1, replication stress (γH2AX expression), and mTOR signaling; the latter revealed by ribosomal S6 protein (rpS6) phosphorylation. All these markers of senescence were distinctly diminished, in a concentration-dependent manner, by Berberine. In view of the evidence that BRB localizes in mitochondria, inhibits respiratory electron chain and activates AMPK, the observed attenuation of the replication stress-induced cellular senescence most likely is mediated by AMPK that leads to inhibition of mTOR signaling. In support of this mechanism is the observation that rhodamine123, the cationic probe targeting mitochondrial electron chain, also suppressed rpS6 phosphorylation. The present findings reveal that: (a) in cells induced to senescence BRB exhibits gero-suppressive properties by means of mTOR/S6 inhibition; (b) in parallel, BRB reduces the level of constitutive DNA damage response, previously shown to report oxidative DNA damage by endogenous ROS; (c) there appears to a causal linkage between the (a) and (b) activities; (d) the in vitro model of premature stress-induced senescence can be used to assess effectiveness of potential gero-suppressive agents targeting mTOR/S6 and ROS signaling; (e) since most of the reported beneficial effects of BRB are in age-relate diseases, it is likely that gero-suppression is the primary activity of this traditional medicine.
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Volume 5, Issue 8

Editorials

Lipid-induced hepatic insulin resistance

Thomas Galbo, Gerald I. Shulman,

GCN2 and TOR converge on aging

Anna Vlanti, Aris Rousakis, Popi Syntichaki,

Why do old flies die?

Michael Rera, Rebecca I. Clark, David W. Walker,

Targeting redox biology to reverse mitochondrial dysfunction

David J. Marcinek, Michael P. Siegel,

p16INK4a in cellular senescence

Elisabeth Simboeck, Luciano Di Croce,

Research Perspective

Rapamycin extends life- and health span because it slows aging

Mikhail V. Blagosklonny,

Research Papers

Serum from humans on long-term calorie restriction enhances stress resistance in cell culture

Daniela Omodei, Danilo Licastro, Francesco Salvatore, Seth D. Crosby, Luigi Fontana,

Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production

Shubhankar Suman, Olga C. Rodriguez, Thomas A. Winters, Albert J. Fornace Jr, Chris Albanese, Kamal Datta,

Berberine suppresses gero-conversion from cell cycle arrest to senescence

Hong Zhao, H Dorota Halicka, Jiangwei Li, Zbigniew Darzynkiewicz,

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