Volume 4, Issue 12

Geropotency: Increased malignant potential of aging neural progenitors

Andrei M. Mikheev, Elizabeth A. Stoll, Rohan Ramakrishna, Svetlana A. Mikheeva, Philip J. Horner, Robert C. Rostomily,

https://doi.org/10.18632/aging.100514 pp 854—855

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Mikheev AM, Stoll EA, Ramakrishna R, Mikheeva SA, Horner PJ, Rostomily RC, . Geropotency: Increased malignant potential of aging neural progenitors. . 4:854-855. https://doi.org/10.18632/aging.100514

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Heat shock response and ionstasis: axis against neurodegeneration

Nikos Kourtis, Vassiliki Nikoletopoulou, Nektarios Tavernarakis,

https://doi.org/10.18632/aging.100517 pp 856—858

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Mitochondria, obesity and aging

Cecile Vernochet, C. Ronald Kahn,

https://doi.org/10.18632/aging.100518 pp 859—860

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Answering the ultimate question “What is the Proximal Cause of Aging?”

Mikhail V. Blagosklonny,

https://doi.org/10.18632/aging.100525 pp 861—877

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Blagosklonny MV, . Answering the ultimate question “What is the Proximal Cause of Aging?”. . 4:861-877. https://doi.org/10.18632/aging.100525

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                TY  - JOUR
                AU  - Blagosklonny, Mikhail V. 
                TI  - Answering the ultimate question “What is the Proximal Cause of Aging?”
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100525
                DO  - 10.18632/aging.100525
                SP  - 861
                EP  - 877
                PY  - 
                AB  - Recent discoveries suggest that aging is neither driven by accumulation of molecular damage of any cause, nor by random damage of any kind. Some predictions of a new theory, quasi-programmed hyperfunction, have already been confirmed and a clinically-available drug slows aging and delays diseases in animals. The relationship between diseases and aging becomes easily apparent. Yet, the essence of aging turns out to be so startling that the theory cannot be instantly accepted and any possible arguments are raised for its disposal. I discuss that these arguments actually support a new theory. Are any questions remaining? And might accumulation of molecular damage still play a peculiar role in aging?
                ER  -

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Embryonic stem cells and inducible pluripotent stem cells: two faces of the same coin?

Francesco Romeo, Francesco Costanzo, Massimiliano Agostini,

https://doi.org/10.18632/aging.100513 pp 878—886

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Romeo F, Costanzo F, Agostini M, . Embryonic stem cells and inducible pluripotent stem cells: two faces of the same coin?. . 4:878-886. https://doi.org/10.18632/aging.100513

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                TY  - JOUR
                AU  - Romeo, Francesco 
                AU  - Costanzo, Francesco 
                AU  - Agostini, Massimiliano 
                TI  - Embryonic stem cells and inducible pluripotent stem cells: two faces of the same coin?
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100513
                DO  - 10.18632/aging.100513
                SP  - 878
                EP  - 886
                PY  - 
                AB  - Embryonic stem cells (ESCs) are derived from the inner cell mass of the blastocysts and are characterized by the ability to renew themselves (self-renewal) and the capability to generate all the cells within the human body. In contrast, inducible pluripotent stem cells (iPSCs) are generated by transfection of four transcription factors in somatic cells. Like embryonic stem cells, they are able to self-renew and differentiate. Because of these features, both ESCs and iPSCs, are under intense clinical investigation for cell-based therapy. In this review, we revisit stem cell biology and add a new layer of complexity. In particular, we will highlight some of the complexities of the system, but also where there may be therapeutic potential for modulation of intrinsic stem cells and where particular caution may be needed in terms of cell transplantation therapies.
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Recent discoveries in the cycling, growing and aging of the p53 field

James A. McCubrey, Zoya N. Demidenko,

https://doi.org/10.18632/aging.100529 pp 887—893

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McCubrey JA, Demidenko ZN, . Recent discoveries in the cycling, growing and aging of the p53 field. . 4:887-893. https://doi.org/10.18632/aging.100529

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                TY  - JOUR
                AU  - McCubrey, James A. 
                AU  - Demidenko, Zoya N. 
                TI  - Recent discoveries in the cycling, growing and aging of the p53 field
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100529
                DO  - 10.18632/aging.100529
                SP  - 887
                EP  - 893
                PY  - 
                AB  - The P53 gene and it product p53 protein is the most studied tumor suppressor, which was considered as oncogene for two decades until 1990. More than 60 thousand papers on the topic of p53 has been abstracted in Pubmed. What yet could be discovered about its role in cell death, growth arrest and apoptosis, as well as a mediator of the therapeutic effect of anticancer drugs. Still during recent few years even more amazing discoveries have been done. Here we review such topics as suppression of epigenetic silencing of a large number of non-coding RNAs, role of p53 in suppression of the senescence phenotype, inhibition of oncogenic metabolism, protection of normal cells from chemotherapy and even tumor suppression without apoptosis and cell cycle arrest.
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One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin

Javier A. Menendez, Jorge Joven,

https://doi.org/10.18632/aging.100523 pp 894—898

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Menendez JA, Joven J, . One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin. . 4:894-898. https://doi.org/10.18632/aging.100523

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                TY  - JOUR
                AU  - Menendez, Javier A. 
                AU  - Joven, Jorge 
                TI  - One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100523
                DO  - 10.18632/aging.100523
                SP  - 894
                EP  - 898
                PY  - 
                AB  - The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs. Here we provide our perspective on recent findings suggesting that de novo biosynthesis of purine nucleotides, which is based on the metabolism of one-carbon compounds, is a new target for metformin's actions at the crossroads of aging and cancer.
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Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging

Olga V. Leontieva, Geraldine M. Paszkiewicz, Mikhail V. Blagosklonny,

https://doi.org/10.18632/aging.100528 pp 899—916

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Leontieva OV, Paszkiewicz GM, Blagosklonny MV, . Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging. . 4:899-916. https://doi.org/10.18632/aging.100528

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                TY  - JOUR
                AU  - Leontieva, Olga V. 
                AU  - Paszkiewicz, Geraldine M. 
                AU  - Blagosklonny, Mikhail V. 
                TI  - Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100528
                DO  - 10.18632/aging.100528
                SP  - 899
                EP  - 916
                PY  - 
                AB  - Males, who are bigger and stronger than females, die younger in most species from flies to mammals including humans. Cellular mass growth is driven in part by mTOR (Target of Rapamycin). When developmental growth is completed, then, instead of growth, mTOR drives aging, manifested by increased cellular functions, such as hyper-secretion by fibroblasts, thus altering homeostasis, leading to age-related diseases and death. We hypothesize that MTOR activity is elevated in male mice compared with females. Noteworthy, 6 months old males were 28 % heavier than females. Also levels of phosphorylated S6 (pS6) and phospho-AKT (p-AKT, Ser 473), markers of the mTOR activity, were higher in male organs tested. Levels of pS6 were highly variable among mice and correlated with body weight and p-AKT. With age, the difference between levels of pS6 between sexes tended to minimize, albeit males still had hyperactive mTOR. Unlike fasting, the intraperitoneal (i.p.) administration of rapamycin eliminated pS6 in all organs of all females measured by immunoblotting and immunohistochemistry without affecting p-AKT and blood insulin. Although i.p. rapamycin dramatically decreased levels of pS6 in males too, it was still detectable by immunoblotting upon longer exposure. Our study demonstrated that both tissue p-AKT and pS6 were higher in young males than young females and were associated with increased body weight and insulin. These data can explain larger body size and faster aging in males. Our data suggest higher efficacy of rapamycin compared to fasting. Higher sensitivity of females to rapamycin may explain more pronounced life extension by rapamycin observed in females compared to males in several studies.
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Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion

Sudha Mannava, Kalyana C. Moparthy, Linda J. Wheeler, Katerina I. Leonova, Joseph A. Wawrzyniak, Anna Bianchi-Smiraglia, Albert E. Berman, Sheryl Flanagan, Donna S. Shewach, Nathalie C. Zeitouni, Andrei V. Gudkov, Christopher K. Mathews, Mikhail A. Nikiforov,

https://doi.org/10.18632/aging.100512 pp 917—922

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Mannava S, Moparthy KC, Wheeler LJ, Leonova KI, Wawrzyniak JA, Bianchi-Smiraglia A, Berman AE, Flanagan S, Shewach DS, Zeitouni NC, Gudkov AV, Mathews CK, Nikiforov MA, . Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion. . 4:917-922. https://doi.org/10.18632/aging.100512

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                TY  - JOUR
                AU  - Mannava, Sudha 
                AU  - Moparthy, Kalyana C. 
                AU  - Wheeler, Linda J. 
                AU  - Leonova, Katerina I. 
                AU  - Wawrzyniak, Joseph A. 
                AU  - Bianchi-Smiraglia, Anna 
                AU  - Berman, Albert E. 
                AU  - Flanagan, Sheryl 
                AU  - Shewach, Donna S. 
                AU  - Zeitouni, Nathalie C. 
                AU  - Gudkov, Andrei V. 
                AU  - Mathews, Christopher K. 
                AU  - Nikiforov, Mikhail A. 
                TI  - Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100512
                DO  - 10.18632/aging.100512
                SP  - 917
                EP  - 922
                PY  - 
                ER  -

Provider: 
                TY  - JOUR
                AU  - Mannava, Sudha 
                AU  - Moparthy, Kalyana C. 
                AU  - Wheeler, Linda J. 
                AU  - Leonova, Katerina I. 
                AU  - Wawrzyniak, Joseph A. 
                AU  - Bianchi-Smiraglia, Anna 
                AU  - Berman, Albert E. 
                AU  - Flanagan, Sheryl 
                AU  - Shewach, Donna S. 
                AU  - Zeitouni, Nathalie C. 
                AU  - Gudkov, Andrei V. 
                AU  - Mathews, Christopher K. 
                AU  - Nikiforov, Mikhail A. 
                TI  - Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100512
                DO  - 10.18632/aging.100512
                SP  - 917
                EP  - 922
                PY  - 
                AB  - The down-regulation of dominant oncogenes, including C-MYC, in tumor cells often leads to the induction of senescence via mechanisms that are not completely identified. In the current study, we demonstrate that MYC-depleted melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase (TS) and ribonucleotide reductase (RR) and subsequent depletion of deoxyribonucleoside triphosphate pools. Simultaneous genetic inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones caused by MYC-depletion. Reciprocally, overexpression of TS and RR in melanoma cells or addition of deoxyribo-nucleosides to culture media substantially inhibited DNA damage and senescence-associated phenotypes caused by C-MYC depletion. Our data demonstrate the essential role of TS and RR in C-MYC-dependent suppression of senescence in melanoma cells.
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P73 and age-related diseases: is there any link with Parkinson Disease?

Francesca Grespi, Gerry Melino,

https://doi.org/10.18632/aging.100515 pp 923—931

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Grespi F, Melino G, . P73 and age-related diseases: is there any link with Parkinson Disease?. . 4:923-931. https://doi.org/10.18632/aging.100515

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                TY  - JOUR
                AU  - Grespi, Francesca 
                AU  - Melino, Gerry 
                TI  - P73 and age-related diseases: is there any link with Parkinson Disease?
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100515
                DO  - 10.18632/aging.100515
                SP  - 923
                EP  - 931
                PY  - 
                AB  - P73 is a member of the p53 transcription factors family with a prominent role in neurobiology, affecting brain development as well as controlling neuronal survival. Accordingly, p73 has been identified as key player in many age-related neurodegenerative diseases, such as Alzheimer's disease, neuroAIDS and Niemann-Pick type C disease. Here we investigate possible correlations of p73 with Parkinson disease. Tyrosine hydroxylase is a crucial player in Parkinson disease being the enzyme necessary for dopamine synthesis. In this work we show that levels of tyrosine hydroxylase can be influenced by p73. We also demonstrate that p73 can protect against tyrosine hydroxylase depletion in an in vitro model of Parkinson disease.
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IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine ‘Bystander senescence’

Sona Hubackova, Katerina Krejcikova, Jiri Bartek, Zdenek Hodny,

https://doi.org/10.18632/aging.100520 pp 932—951

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Hubackova S, Krejcikova K, Bartek J, Hodny Z, . IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine ‘Bystander senescence’. . 4:932-951. https://doi.org/10.18632/aging.100520

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                TY  - JOUR
                AU  - Hubackova, Sona 
                AU  - Krejcikova, Katerina 
                AU  - Bartek, Jiri 
                AU  - Hodny, Zdenek 
                TI  - IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine ‘Bystander senescence’
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100520
                DO  - 10.18632/aging.100520
                SP  - 932
                EP  - 951
                PY  - 
                AB  - Many cancers arise at sites of infection and inflammation. Cellular senescence, a permanent state of cell cycle arrest that provides a barrier against tumorigenesis, is accompanied by elevated proinflammatory cytokines such as IL1, IL6, IL8 and TNFα. Here we demonstrate that media conditioned by cells undergoing any of the three main forms of senescence, i.e. replicative, oncogene- and drug-induced, contain high levels of IL1, IL6, and TGFb capable of inducing reactive oxygen species (ROS)-mediated DNA damage response (DDR). Persistent cytokine signaling and activated DDR evoke senescence in normal bystander cells, accompanied by activation of the JAK/STAT, TGFβ/SMAD and IL1/NFκB signaling pathways. Whereas inhibition of IL6/STAT signaling had no effect on DDR induction in bystander cells, inhibition of either TGFβ/SMAD or IL1/NFκB pathway resulted in decreased ROS production and reduced DDR in bystander cells. Simultaneous inhibition of both TGFβ/SMAD and IL1/NFκB pathways completely suppressed DDR indicating that IL1 and TGFβ cooperate to induce and/or maintain bystander senescence. Furthermore, the observed IL1- and TGFβ-induced expression of NAPDH oxidase Nox4 indicates a mechanistic link between the senescence-associated secretory phenotype (SASP) and DNA damage signaling as a feature shared by development of all major forms of paracrine bystander senescence.
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Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling

H. Dorota Halicka, Hong Zhao, Jiangwei Li, Yong-Syu Lee, Tze-Chen Hsieh, Joseph M. Wu, Zbigniew Darzynkiewicz,

https://doi.org/10.18632/aging.100521 pp 952—965

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Halicka HD, Zhao H, Li J, Lee Y, Hsieh T, Wu JM, Darzynkiewicz Z, . Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. . 4:952-965. https://doi.org/10.18632/aging.100521

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                TY  - JOUR
                AU  - Halicka, H. Dorota 
                AU  - Zhao, Hong 
                AU  - Li, Jiangwei 
                AU  - Lee, Yong-Syu 
                AU  - Hsieh, Tze-Chen 
                AU  - Wu, Joseph M. 
                AU  - Darzynkiewicz, Zbigniew 
                TI  - Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100521
                DO  - 10.18632/aging.100521
                SP  - 952
                EP  - 965
                PY  - 
                AB  - Two different mechanisms are considered to be the primary cause of aging. Cumulative DNA damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Constitutive stimulation of mitogen- and nutrient-sensing mTOR/S6 signaling is the second mechanism (TOR concept). The flow- and laser scanning- cytometric methods were developed to measure the level of the constitutive DNA damage/ROS- as well as of mTOR/S6- signaling in individual cells. Specifically, persistent activation of ATM and expression of γH2AX in untreated cells appears to report constitutive DNA damage induced by endogenous ROS. The level of phosphorylation of Ser235/236-ribosomal protein (RP), of Ser2448-mTOR and of Ser65-4EBP1, informs on constitutive signaling along the mTOR/S6 pathway. Potential gero-suppressive agents rapamycin, metformin, 2-deoxyglucose, berberine, resveratrol, vitamin D3 and aspirin, all decreased the level of constitutive DNA damage signaling as seen by the reduced expression of γH2AX in proliferating A549, TK6, WI-38 cells and in mitogenically stimulated human lymphocytes. They all also decreased the level of intracellular ROS and mitochondrial trans-membrane potential ΔΨm, the marker of mitochondrial energizing as well as reduced phosphorylation of mTOR, RP-S6 and 4EBP1. The most effective was rapamycin. Although the primary target of each on these agents may be different the data are consistent with the downstream mechanism in which the decline in mTOR/S6K signaling and translation rate is coupled with a decrease in oxidative phosphorylation, (revealed by ΔΨm) that leads to reduction of ROS and oxidative DNA damage. The decreased rate of translation induced by these agents may slow down cells hypertrophy and alleviate other features of cell aging/senescence. Reduction of oxidative DNA damage may lower predisposition to neoplastic transformation which otherwise may result from errors in repair of DNA sites coding for oncogenes or tumor suppressor genes. The data suggest that combined assessment of constitutive γH2AX expression, mitochondrial activity (ROS, ΔΨm) and mTOR signaling provides an adequate gamut of cell responses to evaluate effectiveness of gero-suppressive agents.
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Complete cardiac regeneration in a mouse model of myocardial infarction

Bernhard Johannes Haubner, Martyna Adamowicz-Brice, Sanjay Khadayate, Viktoria Tiefenthaler, Bernhard Metzler, Tim Aitman, Josef M. Penninger,

https://doi.org/10.18632/aging.100526 pp 966—977

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Haubner BJ, Adamowicz-Brice M, Khadayate S, Tiefenthaler V, Metzler B, Aitman T, Penninger JM, . Complete cardiac regeneration in a mouse model of myocardial infarction. . 4:966-977. https://doi.org/10.18632/aging.100526

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                TY  - JOUR
                AU  - Haubner, Bernhard Johannes 
                AU  - Adamowicz-Brice, Martyna 
                AU  - Khadayate, Sanjay 
                AU  - Tiefenthaler, Viktoria 
                AU  - Metzler, Bernhard 
                AU  - Aitman, Tim 
                AU  - Penninger, Josef M. 
                TI  - Complete cardiac regeneration in a mouse model of myocardial infarction
                JO  - 
                JA  - 
                VL  - 4
                IS  - 12
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100526
                DO  - 10.18632/aging.100526
                SP  - 966
                EP  - 977
                PY  - 
                AB  - Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients.
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Volume 4, Issue 12

Editorials

Geropotency: Increased malignant potential of aging neural progenitors

Andrei M. Mikheev, Elizabeth A. Stoll, Rohan Ramakrishna, Svetlana A. Mikheeva, Philip J. Horner, Robert C. Rostomily,

Heat shock response and ionstasis: axis against neurodegeneration

Nikos Kourtis, Vassiliki Nikoletopoulou, Nektarios Tavernarakis,

Mitochondria, obesity and aging

Cecile Vernochet, C. Ronald Kahn,

Reviews

Answering the ultimate question “What is the Proximal Cause of Aging?”

Mikhail V. Blagosklonny,

Embryonic stem cells and inducible pluripotent stem cells: two faces of the same coin?

Francesco Romeo, Francesco Costanzo, Massimiliano Agostini,

Recent discoveries in the cycling, growing and aging of the p53 field

James A. McCubrey, Zoya N. Demidenko,

Research Perspective

One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin

Javier A. Menendez, Jorge Joven,

Research Papers

Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging

Olga V. Leontieva, Geraldine M. Paszkiewicz, Mikhail V. Blagosklonny,

Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion

Sudha Mannava, Kalyana C. Moparthy, Linda J. Wheeler, Katerina I. Leonova, Joseph A. Wawrzyniak, Anna Bianchi-Smiraglia, Albert E. Berman, Sheryl Flanagan, Donna S. Shewach, Nathalie C. Zeitouni, Andrei V. Gudkov, Christopher K. Mathews, Mikhail A. Nikiforov,

P73 and age-related diseases: is there any link with Parkinson Disease?

Francesca Grespi, Gerry Melino,

IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine ‘Bystander senescence’

Sona Hubackova, Katerina Krejcikova, Jiri Bartek, Zdenek Hodny,

Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling

H. Dorota Halicka, Hong Zhao, Jiangwei Li, Yong-Syu Lee, Tze-Chen Hsieh, Joseph M. Wu, Zbigniew Darzynkiewicz,

Complete cardiac regeneration in a mouse model of myocardial infarction

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