Volume 8, Issue 10

Perridon BW, Leuvenink HG, Hillebrands J, van Goor H, Bos EM, . The role of hydrogen sulfide in aging and age-related pathologies. . 8:2264-2289. https://doi.org/10.18632/aging.101026

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                TY  - JOUR
                AU  - Perridon, Bernard W.
                AU  - Leuvenink, Henri G.D.
                AU  - Hillebrands, Jan-Luuk 
                AU  - van Goor, Harry 
                AU  - Bos, Eelke M.
                TI  - The role of hydrogen sulfide in aging and age-related pathologies
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101026
                DO  - 10.18632/aging.101026
                SP  - 2264
                EP  - 2289
                PY  - 
                AB  - When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the ‘hallmarks of aging’. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H2S) in the regulation of aging. Nowadays, H2S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H2S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies.
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The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis

Munehiro Kitada, Yoshio Ogura, Daisuke Koya,

https://doi.org/10.18632/aging.101068 pp 2290—2307

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Kitada M, Ogura Y, Koya D, . The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. . 8:2290-2307. https://doi.org/10.18632/aging.101068

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                TY  - JOUR
                AU  - Kitada, Munehiro 
                AU  - Ogura, Yoshio 
                AU  - Koya, Daisuke 
                TI  - The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101068
                DO  - 10.18632/aging.101068
                SP  - 2290
                EP  - 2307
                PY  - 
                AB  - Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.
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SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation

Ganye Zhao, Hui Wang, Chenzhong Xu, Pan Wang, Jun Chen, Pengfeng Wang, Zhaomeng Sun, Yuanyuan Su, Zhao Wang, Limin Han, Tanjun Tong,

https://doi.org/10.18632/aging.101038 pp 2308—2323

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Zhao G, Wang H, Xu C, Wang P, Chen J, Wang P, Sun Z, Su Y, Wang Z, Han L, Tong T, . SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation. . 8:2308-2323. https://doi.org/10.18632/aging.101038

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                TY  - JOUR
                AU  - Zhao, Ganye 
                AU  - Wang, Hui 
                AU  - Xu, Chenzhong 
                AU  - Wang, Pan 
                AU  - Chen, Jun 
                AU  - Wang, Pengfeng 
                AU  - Sun, Zhaomeng 
                AU  - Su, Yuanyuan 
                AU  - Wang, Zhao 
                AU  - Han, Limin 
                AU  - Tong, Tanjun 
                TI  - SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101038
                DO  - 10.18632/aging.101038
                SP  - 2308
                EP  - 2323
                PY  - 
                AB  - Sirtuin6(SIRT6) has been implicated as a key factor in aging and aging-related diseases. However, the role of SIRT6 in cellular senescence has not been fully understood. Here, we show that SIRT6 repressed the expression of p27Kip1 (p27) in cellular senescence. The expression of SIRT6 was reduced during cellular senescence, whereas enforced SIRT6 expression promoted cell proliferation and antagonized cellular senescence. In addition, we demonstrated that SIRT6 promoted p27 degradation by proteasome and SIRT6 decreased the acetylation level and protein half-life of p27. p27 acetylation increased its protein stability. Furthermore, SIRT6 directly interacted with p27. Importantly, p27 was strongly acetylated and had a prolonged protein half-life with the reduction of SIRT6 when cells were senescent, compared with those young cells. Finally, SIRT6 markedly rescued senescence induced by p27. Our findings indicate that SIRT6 decreases p27 acetylation, leading to its degradation via ubiquitin-proteasome pathway and then delays cellular senescence.
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A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1

Dahai Liu, Qiang Zhang, Hong Zhang, Ling Tang, Wei Li, Dongming Zhang, Guoying Wu, Shoudong Ye, Qian Ban, Kan He,

https://doi.org/10.18632/aging.101049 pp 2324—2336

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Liu D, Zhang Q, Zhang H, Tang L, Li W, Zhang D, Wu G, Ye S, Ban Q, He K, . A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1. . 8:2324-2336. https://doi.org/10.18632/aging.101049

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                TY  - JOUR
                AU  - Liu, Dahai 
                AU  - Zhang, Qiang 
                AU  - Zhang, Hong 
                AU  - Tang, Ling 
                AU  - Li, Wei 
                AU  - Zhang, Dongming 
                AU  - Wu, Guoying 
                AU  - Ye, Shoudong 
                AU  - Ban, Qian 
                AU  - He, Kan 
                TI  - A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101049
                DO  - 10.18632/aging.101049
                SP  - 2324
                EP  - 2336
                PY  - 
                AB  - The mutation of somitogenesis protein Mesogenin 1 (Msgn1) has been widely used to study the direct link between somitogenesis and the development of an embryo. Several studies have used gene expression profiling of somitogenesis to identify the key genes in the process, but few have focused on the pathways involved and the coexpression patterns of associated pathways. Here we employed time-course microarray datasets of differentiating embryonic stem cells by overexpressing the transcription factor Msgn1 from the public database library of Gene Expression Omnibus (GEO). Then we applied gene set enrichment analysis (GSEA) to the datasets and performed candidate transcription factors selection. As a result, several significantly regulated pathways and transcription factors (TFs), as well as some of the specific signaling pathways, were identified during somitogenesis under Msgn1 overexpression, most of which had not been reported previously. Finally, significant core genes such as Hes1 and Notch1 as well as some of the TFs such as PPARs and FOXs were identified to construct coexpression networks of related pathways, the expression patterns of which had been validated by our following quantitative real-time PCR (qRT-PCR). The results of our study may help us better understand the molecular mechanisms of somitogenesis in mice at the genome-wide level.
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TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response

Zhi-Yuan Li, Zhao-Li Chen, Ting Zhang, Chao Wei, Wei-Yun Shi,

https://doi.org/10.18632/aging.101050 pp 2337—2354

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Li Z, Chen Z, Zhang T, Wei C, Shi W, . TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response. . 8:2337-2354. https://doi.org/10.18632/aging.101050

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                TY  - JOUR
                AU  - Li, Zhi-Yuan 
                AU  - Chen, Zhao-Li 
                AU  - Zhang, Ting 
                AU  - Wei, Chao 
                AU  - Shi, Wei-Yun 
                TI  - TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101050
                DO  - 10.18632/aging.101050
                SP  - 2337
                EP  - 2354
                PY  - 
                AB  - The corneal epithelium plays important roles in the maintenance of corneal transparency for good vision, and acts as a protective barrier against foreign insults. Structural and functional changes with aging in the corneal epithelium have been documented. Here we found that transforming growth factor-β (TGF-β) is highly expressed in the elderly donor corneal epithelium, as are senescence-associated genes, such as p16 and p21. In human corneal epithelial cell (HCEC) models, TGF-β induces cellular senescence, characterized by increased SA-β-gal positive cells and elevated expression of p16 and p21. Pharmacological inhibition of TGF-β signaling alleviates TGF-β-induced cellular senescence. In addition, we determined that senescence-associated inflammation was significantly aggravated in TGF-β-induced cellular senescence by detecting the expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNFα). Both genetic and pharmacological approaches revealed that blocking nuclear factor-κB (NF-κB) signaling not only inhibited the production of inflammatory factors, but also rescued the senescent phenotype induced by TGF-β in HCECs. Mechanistically, TGF-β induced an atypical RNA stress responses, leading to accelerated mRNA degradation of IκBα, an inhibitor of NF-κB. Together, our data indicate that TGF-β-driven NF-κB activation contributes to corneal epithelial senescence via RNA metabolism and the inflammation blockade can attenuate TGF-β-induced senescence.
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Caveolin-1 controls mitochondrial function through regulation of m-AAA mitochondrial protease

Daniela Volonte, Zhongmin Liu, Sruti Shiva, Ferruccio Galbiati,

https://doi.org/10.18632/aging.101051 pp 2355—2369

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Volonte D, Liu Z, Shiva S, Galbiati F, . Caveolin-1 controls mitochondrial function through regulation of m-AAA mitochondrial protease. . 8:2355-2369. https://doi.org/10.18632/aging.101051

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Provider: 
 TY - JOUR
 AU - Volonte, Daniela 
 AU - Liu, Zhongmin 
 AU - Shiva, Sruti 
 AU - Galbiati, Ferruccio 
 TI - Caveolin-1 controls mitochondrial function through regulation of m-AAA mitochondrial protease
 JO - 
 JA - 
 VL - 8
 IS - 10
 PB - 
 SN - 
 UR - https://doi.org/10.18632/aging.101051
 DO - 10.18632/aging.101051
 SP - 2355
 EP - 2369
 PY - 
 AB - Mitochondrial proteases ensure mitochondrial integrity and function after oxidative stress by providing mitochondrial protein quality control. However, the molecular mechanisms that regulate this basic biological function in eukaryotic cells remain largely unknown. Caveolin-1 is a scaffolding protein involved in signal transduction. We find that AFG3L2, a m-AAA type of mitochondrial protease, is a novel caveolin-1-interacting protein in vitro. We show that oxidative stress promotes the translocation of both caveolin-1 and AFG3L2 to mitochondria, enhances the interaction of caveolin-1 with AFG3L2 in mitochondria and stimulates mitochondrial protease activity in wild-type fibroblasts. Localization of AFG3L2 to mitochondria after oxidative stress is inhibited in fibroblasts lacking caveolin-1, which results in impaired mitochondrial protein quality control, an oxidative phosphorylation to aerobic glycolysis switch and reduced ATP production. Mechanistically, we demonstrate that a lack of caveolin-1 does not alter either mitochondrial number or morphology but leads to the cytoplasmic and proteasome-dependent degradation of complexes I, III, IV and V upon oxidant stimulation. Restoration of mitochondrial respiratory chain complexes in caveolin-1 null fibroblasts reverts the enhanced glycolysis observed in these cells. Expression of a mutant form of AFG3L2, which has reduced affinity for caveolin-1, fails to localize to mitochondria and promotes degradation of complex IV after oxidative stress. Thus, caveolin-1 maintains mitochondrial integrity and function when cells are challenged with free radicals by promoting the mitochondrial localization of m-AAA protease and its quality control functions.
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A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated

Kathleen E. Fischer, Jessica M. Hoffman, Lauren B. Sloane, Jonathan A.L. Gelfond, Vanessa Y. Soto, Arlan G. Richardson, Steven N. Austad,

https://doi.org/10.18632/aging.101059 pp 2370—2391

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Fischer KE, Hoffman JM, Sloane LB, Gelfond JA, Soto VY, Richardson AG, Austad SN, . A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated. . 8:2370-2391. https://doi.org/10.18632/aging.101059

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                TY  - JOUR
                AU  - Fischer, Kathleen E. 
                AU  - Hoffman, Jessica M. 
                AU  - Sloane, Lauren B. 
                AU  - Gelfond, Jonathan A.L. 
                AU  - Soto, Vanessa Y. 
                AU  - Richardson, Arlan G. 
                AU  - Austad, Steven N. 
                TI  - A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101059
                DO  - 10.18632/aging.101059
                SP  - 2370
                EP  - 2391
                PY  - 
                AB  - Lifespan provides a discrete metric that is intuitively appealing and the assumption has been that healthspan is extended concomitant with lifespan. Medicine has been more successful at extending life than preserving health during aging. Interventions that extend lifespan in model organisms do not always result in a corresponding increase in healthspan, suggesting that lifespan and healthspan may be uncoupled. To understand how interventions that extend life affect healthspan, we need measures that distinguish between young and old animals. Here we measured age-related changes in healthspan in male and female C57BL/6JNia mice assessed at 4 distinct ages (4 months, 20 months, 28 months and 32 months). Correlations between health parameters and age varied. Some parameters show consistent patterns with age across studies and in both sexes, others changed in one sex only and others showed no significant differences in mice of different ages. Few correlations existed among health assays, suggesting that physiological function in domains we assessed change independently in aging mice. With one exception, health parameters were not significantly associated with an increased probability of premature death. Our results show the need for more robust measures of murine health and suggest a potential disconnect between health and lifespan in mice.
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Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice

Joohwee Kim, Vivek Vaish, Mingxiao Feng, Kevin Field, Ioulia Chatzistamou, Minsub Shim,

https://doi.org/10.18632/aging.101060 pp 2392—2406

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Kim J, Vaish V, Feng M, Field K, Chatzistamou I, Shim M, . Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice. . 8:2392-2406. https://doi.org/10.18632/aging.101060

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                TY  - JOUR
                AU  - Kim, Joohwee 
                AU  - Vaish, Vivek 
                AU  - Feng, Mingxiao 
                AU  - Field, Kevin 
                AU  - Chatzistamou, Ioulia 
                AU  - Shim, Minsub 
                TI  - Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101060
                DO  - 10.18632/aging.101060
                SP  - 2392
                EP  - 2406
                PY  - 
                AB  - Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders.
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Height indicates hematopoietic capacity in elderly Japanese men

Yuji Shimizu, Shimpei Sato, Jun Koyamatsu, Hirotomo Yamanashi, Mako Nagayoshi, Koichiro Kadota, Takahiro Maeda,

https://doi.org/10.18632/aging.101061 pp 2407—2413

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Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, Maeda T, . Height indicates hematopoietic capacity in elderly Japanese men. . 8:2407-2413. https://doi.org/10.18632/aging.101061

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                TY  - JOUR
                AU  - Shimizu, Yuji 
                AU  - Sato, Shimpei 
                AU  - Koyamatsu, Jun 
                AU  - Yamanashi, Hirotomo 
                AU  - Nagayoshi, Mako 
                AU  - Kadota, Koichiro 
                AU  - Maeda, Takahiro 
                TI  - Height indicates hematopoietic capacity in elderly Japanese men
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101061
                DO  - 10.18632/aging.101061
                SP  - 2407
                EP  - 2413
                PY  - 
                AB  - Previously, we reported that height is an indicator of the capacity of vascular repair in elderly men, especially hypertensive men. On the other hand, hemoglobin could act as a possible biochemical index of hypertension-induced vascular damage. However, no studies have clarified the correlation between height and hematopoietic activity. We conducted a cross-sectional study of 249 men aged 65-69 undergoing a general health check-up. Reticulocyte was used to evaluate hematopoietic activity. Because hemoglobin concentration should influence hematopoietic activity, analyses stratified by hemoglobin level were performed. Independent of known cardiovascular risk factors and other hematological parameters (white blood cell count), a significant positive correlation was seen between height and reticulocytes for total subjects and subjects with a high hemoglobin concentration (≥14.5 g/dL), but not in subjects with a low hemoglobin concentration (&lt;14.5 g/dL). The standardized parameter estimates (β) were β=0.18, p=0.003 for total subjects, β=0.28, p=0.001 for subjects with a high hemoglobin concentration, and β=0.03, p=0.717 for subjects with low hemoglobin. Independently, height is significantly positively correlated with reticulocyte in elderly Japanese men, particularly in men with a high hemoglobin concentration. These results indicate that subjects with a short stature might have lower hematopoietic capacity than those with a high stature.
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Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function

Leland Perice, Nir Barzilai, Joe Verghese, Erica F. Weiss, Roee Holtzer, Pinchas Cohen, Sofiya Milman,

https://doi.org/10.18632/aging.101063 pp 2414—2424

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Perice L, Barzilai N, Verghese J, Weiss EF, Holtzer R, Cohen P, Milman S, . Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function. . 8:2414-2424. https://doi.org/10.18632/aging.101063

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                TY  - JOUR
                AU  - Perice, Leland 
                AU  - Barzilai, Nir 
                AU  - Verghese, Joe 
                AU  - Weiss, Erica F. 
                AU  - Holtzer, Roee 
                AU  - Cohen, Pinchas 
                AU  - Milman, Sofiya 
                TI  - Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101063
                DO  - 10.18632/aging.101063
                SP  - 2414
                EP  - 2424
                PY  - 
                AB  - Mutations that reduce somatotropic signaling result in improved lifespan and health-span in model organisms and humans. However, whether reduced circulating insulin-like growth factor-I (IGF-I) level is detrimental to cognitive and muscle function in older adults remains understudied. A cross-sectional analysis was performed in Ashkenazi Jews with exceptional longevity (age ≥95 years). Cognition was assessed using the Mini-Mental State Examination and muscle function with the chair rise test, grip-strength, and gait speed. Muscle mass was estimated using the skeletal muscle index. Serum IGF-I was measured with liquid chromatography mass spectrometry. In gender stratified age-adjusted logistic regression analysis, females with IGF-I levels in the first tertile had lower odds of being cognitively impaired compared to females with IGF-I levels within the upper two tertiles, OR (95% CI) 0.39 (0.19-0.82). The result remained significant after adjustment for multiple parameters. No significant association was identified in males between IGF-I and cognition. No relationship was found between IGF-I tertiles and muscle function and muscle mass in females or males. Lower circulating IGF-I is associated with better cognitive function in females with exceptional longevity, with no detriment to skeletal muscle mass and function.
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Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration

Amelia Pollard, Freya Shephard, James Freed, Susan Liddell, Lisa Chakrabarti,

https://doi.org/10.18632/aging.101064 pp 2425—2436

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Pollard A, Shephard F, Freed J, Liddell S, Chakrabarti L, . Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. . 8:2425-2436. https://doi.org/10.18632/aging.101064

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                TY  - JOUR
                AU  - Pollard, Amelia 
                AU  - Shephard, Freya 
                AU  - Freed, James 
                AU  - Liddell, Susan 
                AU  - Chakrabarti, Lisa 
                TI  - Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101064
                DO  - 10.18632/aging.101064
                SP  - 2425
                EP  - 2436
                PY  - 
                AB  - Carbonic anhydrase inhibitors are used to treat glaucoma and cancers. Carbonic anhydrases perform a crucial role in the conversion of carbon dioxide and water into bicarbonate and protons. However, there is little information about carbonic anhydrase isoforms during the process of ageing. Mitochondrial dysfunction is implicit in ageing brain and muscle. We have interrogated isolated mitochondrial fractions from young adult and middle aged mouse brain and skeletal muscle. We find an increase of tissue specific carbonic anhydrases in mitochondria from middle-aged brain and skeletal muscle. Mitochondrial carbonic anhydrase II was measured in the Purkinje cell degeneration (pcd5J) mouse model. In pcd5J we find mitochondrial carbonic anhydrase II is also elevated in brain from young adults undergoing a process of neurodegeneration. We show C.elegans exposed to carbonic anhydrase II have a dose related shorter lifespan suggesting that high CAII levels are in themselves life limiting. We show for the first time that the mitochondrial content of brain and skeletal tissue are exposed to significantly higher levels of active carbonic anhydrases as early as in middle-age. Carbonic anhydrases associated with mitochondria could be targeted to specifically modulate age related impairments and disease.
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Clustering of geriatric deficits emerges to be an essential feature of ageing - results of a cross-sectional study in Poland

Karolina Piotrowicz, Agnieszka Pac, Anna Barbara Skalska, Jerzy Chudek, Alicja Klich-Rączka, Aleksandra Szybalska, Jean-Pierre Michel, Tomasz Grodzicki,

https://doi.org/10.18632/aging.101055 pp 2437—2448

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Piotrowicz K, Pac A, Skalska AB, Chudek J, Klich-Rączka A, Szybalska A, Michel J, Grodzicki T, . Clustering of geriatric deficits emerges to be an essential feature of ageing - results of a cross-sectional study in Poland. . 8:2437-2448. https://doi.org/10.18632/aging.101055

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                TY  - JOUR
                AU  - Piotrowicz, Karolina 
                AU  - Pac, Agnieszka 
                AU  - Skalska, Anna Barbara 
                AU  - Chudek, Jerzy 
                AU  - Klich-Rączka, Alicja 
                AU  - Szybalska, Aleksandra 
                AU  - Michel, Jean-Pierre 
                AU  - Grodzicki, Tomasz 
                TI  - Clustering of geriatric deficits emerges to be an essential feature of ageing - results of a cross-sectional study in Poland
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101055
                DO  - 10.18632/aging.101055
                SP  - 2437
                EP  - 2448
                PY  - 
                AB  - The majority of old people suffer from various clinical conditions that affect health, functioning and quality of life. This research is a part of a cross-sectional, nationwide PolSenior Study that provides a comprehensive assessment of eight geriatric impairments and their co-occurrence in a representative sample (3471 participant aged 65-104 years, mean age 78.3 years) of the old adults living in the community in Poland. The participants were recruited randomly from all administrative regions of Poland by a three-stage, proportional, stratified-by-age group selection process. Eight geriatric conditions were assessed: falls, incontinences, cognitive impairment, mood disorders, vision and hearing impairments, malnutrition, and functional dependence. We showed that the most common deficits causing disability were vision and hearing impairments, and mood disorders, with more than two thirds of the participants presented at least one geriatric deficit. We showed that presence any of the analyzed conditions significantly increased the risk for co-occurrence of other examined weaknesses. The highest prevalence odds ratios were for functional dependence and, respectively: malnutrition (8.61, 95%CI:4.70-15.80), incontinences (8.0, 95%CI:5.93-10.70), and cognitive impairment (7.22; 95%CI:5.91-8.83). We concluded that the majority of the old people living in the community present various clinical conditions that prompt disability.
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Inducing cellular senescence in vitro by using genetically encoded photosensitizers

Nadezhda V. Petrova, Artem V. Luzhin, Ekaterina O. Serebrovskaya, Alina P. Ryumina, Artem K. Velichko, Sergey V. Razin, Omar L. Kantidze,

https://doi.org/10.18632/aging.101065 pp 2449—2462

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Petrova NV, Luzhin AV, Serebrovskaya EO, Ryumina AP, Velichko AK, Razin SV, Kantidze OL, . Inducing cellular senescence in vitro by using genetically encoded photosensitizers. . 8:2449-2462. https://doi.org/10.18632/aging.101065

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Provider: 
 TY - JOUR
 AU - Petrova, Nadezhda V. 
 AU - Luzhin, Artem V. 
 AU - Serebrovskaya, Ekaterina O. 
 AU - Ryumina, Alina P. 
 AU - Velichko, Artem K. 
 AU - Razin, Sergey V. 
 AU - Kantidze, Omar L. 
 TI - Inducing cellular senescence in vitro by using genetically encoded photosensitizers
 JO - 
 JA - 
 VL - 8
 IS - 10
 PB - 
 SN - 
 UR - https://doi.org/10.18632/aging.101065
 DO - 10.18632/aging.101065
 SP - 2449
 EP - 2462
 PY - 
 AB - Cellular senescence, a form of cell cycle arrest, is one of the cellular responses to different types of exogenous and endogenous damage. The senescence phenotype can be induced in vitro by oncogene overexpression and/or DNA damage. Recently, we have reported a novel mechanism of cellular senescence induction by mild genotoxic stress. Specifically, we have shown that the formation of a small number of DNA lesions in normal and cancer cells during S phase leads to cellular senescence-like arrest within the same cell cycle. Here, based on this mechanism, we suggest an approach to remotely induce premature senescence in human cell cultures using short-term light irradiation. We used the genetically encoded photosensitizers, tandem KillerRed and miniSOG, targeted to chromatin by fusion to core histone H2B to induce moderate levels of DNA damage by light in S phase cells. We showed that the cells that express the H2B-fused photosensitizers acquire a senescence phenotype upon illumination with the appropriate light source. Furthermore, we demonstrated that both chromatin-targeted tandem KillerRed (produces O2¯) and miniSOG (produces 1O2) induce single-stranded DNA breaks upon light illumination. Interestingly, miniSOG was also able to induce double-stranded DNA breaks.
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Plasticity Related Gene 3 (PRG3) overcomes myelin-associated growth inhibition and promotes functional recovery after spinal cord injury

Thomas Broggini, Lisa Schnell, Ali Ghoochani, José María Mateos, Michael Buchfelder, Kurt Wiendieck, Michael K. Schäfer, Ilker Y. Eyupoglu, Nicolai E. Savaskan,

https://doi.org/10.18632/aging.101066 pp 2463—2487

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Broggini T, Schnell L, Ghoochani A, Mateos JM, Buchfelder M, Wiendieck K, Schäfer MK, Eyupoglu IY, Savaskan NE, . Plasticity Related Gene 3 (PRG3) overcomes myelin-associated growth inhibition and promotes functional recovery after spinal cord injury. . 8:2463-2487. https://doi.org/10.18632/aging.101066

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                TY  - JOUR
                AU  - Broggini, Thomas 
                AU  - Schnell, Lisa 
                AU  - Ghoochani, Ali 
                AU  - Mateos, José María 
                AU  - Buchfelder, Michael 
                AU  - Wiendieck, Kurt 
                AU  - Schäfer, Michael K. 
                AU  - Eyupoglu, Ilker Y. 
                AU  - Savaskan, Nicolai E. 
                TI  - Plasticity Related Gene 3 (PRG3) overcomes myelin-associated growth inhibition and promotes functional recovery after spinal cord injury
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101066
                DO  - 10.18632/aging.101066
                SP  - 2463
                EP  - 2487
                PY  - 
                AB  - The Plasticity Related Gene family covers five, brain-specific, transmembrane proteins (PRG1-5, also termed LPPR1-5) that operate in neuronal plasticity during development, aging and brain trauma. Here we investigated the role of the PRG family on axonal and filopodia outgrowth. Comparative analysis revealed the strongest outgrowth induced by PRG3 (LPPR1). During development, PRG3 is ubiquitously located at the tip of neuronal processes and at the plasma membrane and declines with age. In utero electroporation of PRG3 induced dendritic protrusions and accelerated spine formations in cortical pyramidal neurons. The neurite growth promoting activity of PRG3 requires RasGRF1 (RasGEF1/Cdc25) mediated downstream signaling. Moreover, in axon collapse assays, PRG3-induced neurites resisted growth inhibitors such as myelin, Nogo-A (Reticulon/RTN-4), thrombin and LPA and impeded the RhoA-Rock-PIP5K induced neurite repulsion. Transgenic adult mice with constitutive PRG3 expression displayed strong axonal sprouting distal to a spinal cord lesion. Moreover, fostered PRG3 expression promoted complex motor-behavioral recovery compared to wild type controls as revealed in the Schnell swim test (SST). Thus, PRG3 emerges as a developmental RasGRF1-dependent conductor of filopodia formation and axonal growth enhancer. PRG3-induced neurites resist brain injury-associated outgrowth inhibitors and contribute to functional recovery after spinal cord lesions. Here, we provide evidence that PRG3 operates as an essential neuronal growth promoter in the nervous system. Maintaining PRG3 expression in aging brain may turn back the developmental clock for neuronal regeneration and plasticity.
                ER  -

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Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Thomas Walker, Christos Michaelides, Antigoni Ekonomou, Kalotina Geraki, Harold G Parkes, Maria Suessmilch, Amy H Herlihy, William R Crum, Po-Wah So,

https://doi.org/10.18632/aging.101069 pp 2488—2508

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Walker T, Michaelides C, Ekonomou A, Geraki K, Parkes HG, Suessmilch M, Herlihy AH, Crum WR, So P, . Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction. . 8:2488-2508. https://doi.org/10.18632/aging.101069

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                TY  - JOUR
                AU  - Walker, Thomas 
                AU  - Michaelides, Christos 
                AU  - Ekonomou, Antigoni 
                AU  - Geraki, Kalotina 
                AU  - Parkes, Harold G 
                AU  - Suessmilch, Maria 
                AU  - Herlihy, Amy H 
                AU  - Crum, William R 
                AU  - So, Po-Wah 
                TI  - Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101069
                DO  - 10.18632/aging.101069
                SP  - 2488
                EP  - 2508
                PY  - 
                AB  - Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN). The unexpected dissociation of iron accumulation from ferritin-upregulation in the SN suggests iron dyshomeostasis in the SN. Occurring alongside microgliosis and astrogliosis, iron dyshomeotasis may contribute to the particular vulnerability of the SN. Dietary restriction (DR) has long been touted to ameliorate brain aging and we show DR attenuated age-related in vivo R2 increases in the SN over ages 7 – 19 months, concomitant with normal iron-induction of ferritin expression and decreased microgliosis. Iron is known to induce microgliosis and conversely, microgliosis can induce iron accumulation, which of these may be the initial pathological aging event warrants further investigation. We suggest iron chelation therapies and anti-inflammatory treatments may be putative ‘anti-brain aging’ therapies and combining these strategies may be synergistic.
                ER  -

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MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway

Cheng-Cao Sun, Shu-Jun Li, Zhan-Peng Yuan, De-Jia Li,

https://doi.org/10.18632/aging.101080 pp 2509—2524

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Sun C, Li S, Yuan Z, Li D, . MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway. . 8:2509-2524. https://doi.org/10.18632/aging.101080

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                TY  - JOUR
                AU  - Sun, Cheng-Cao 
                AU  - Li, Shu-Jun 
                AU  - Yuan, Zhan-Peng 
                AU  - Li, De-Jia 
                TI  - MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101080
                DO  - 10.18632/aging.101080
                SP  - 2509
                EP  - 2524
                PY  - 
                AB  - Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.
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Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

Amiya Kumar Ghosh, Theresa Mau, Martin O’Brien, Sanjay Garg, Raymond Yung,

https://doi.org/10.18632/aging.101083 pp 2525—2537

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Ghosh AK, Mau T, O’Brien M, Garg S, Yung R, . Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue. . 8:2525-2537. https://doi.org/10.18632/aging.101083

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                TY  - JOUR
                AU  - Ghosh, Amiya Kumar 
                AU  - Mau, Theresa 
                AU  - O’Brien, Martin 
                AU  - Garg, Sanjay 
                AU  - Yung, Raymond 
                TI  - Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101083
                DO  - 10.18632/aging.101083
                SP  - 2525
                EP  - 2537
                PY  - 
                AB  - Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort. Elevated expressions of ER-stress marker CHOP and autophagy substrate SQSTM1/p62 are observed in old SVFs compared to young, when treated with either vehicle or with thapsigargin (Tg), an ER stress inducer. Treatment with bafilomycin A1 (Baf), a vacuolar-type H (+)-ATPase, or Tg elevated expressions of CHOP, and SQSTM1/p62 and LC-3-II, in 3T3-L1-preadipocytes. We also demonstrate impaired autophagy activity in old SVFs by analyzing increased accumulation of autophagy substrates LC3-II and p62. Compromised autophagy activity in old SVFs is correlated with enhanced release of pro-inflammatory cytokines IL-6 and MCP-1. Finally, SVFs from calorie restricted old mice (CR-O) have shown enhanced autophagy activity compared to ad libitum fed old mice (AL-O). Our results support the notion that diminished autophagy activity with aging contributes to increased adipose tissue ER stress and inflammation.
                ER  -

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Prenatal hyperbaric normoxia treatment improves healthspan and regulates chitin metabolic genes in Drosophila melanogaster

Suyeun Yu, Eunil Lee, Bodokhsuren Tsogbadrakh, Gwang-Ic Son, Mari Kim,

https://doi.org/10.18632/aging.101084 pp 2538—2550

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Yu S, Lee E, Tsogbadrakh B, Son G, Kim M, . Prenatal hyperbaric normoxia treatment improves healthspan and regulates chitin metabolic genes in Drosophila melanogaster. . 8:2538-2550. https://doi.org/10.18632/aging.101084

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Provider: 
 TY - JOUR
 AU - Yu, Suyeun 
 AU - Lee, Eunil 
 AU - Tsogbadrakh, Bodokhsuren 
 AU - Son, Gwang-Ic 
 AU - Kim, Mari 
 TI - Prenatal hyperbaric normoxia treatment improves healthspan and regulates chitin metabolic genes in Drosophila melanogaster
 JO - 
 JA - 
 VL - 8
 IS - 10
 PB - 
 SN - 
 UR - https://doi.org/10.18632/aging.101084
 DO - 10.18632/aging.101084
 SP - 2538
 EP - 2550
 PY - 
 AB - Aging is a universal, irreversible process accompanied by physiological declines that culminate in death. Rapid progress in gerontology research has revealed that aging can be slowed through mild stress-induced hormesis. We previously reported that hyperbaric normoxia (HN, 2 atm absolute pressure with 10% O2) induces a cytoprotective response in vitro by regulating fibronectin. In the present study, we investigated the hormetic effects of prenatal HN exposure on Drosophila healthspan related to molecular defense mechanisms. HN exposure had no disruptive effect on developmental rate or adult body weight. However, lifespan was clearly enhanced, as was resistance to oxidative and heat stress. In addition, levels of reactive oxygen species were significantly decreased and motor performance was increased. HN stress has been shown to trigger molecular changes in the heat shock response and ROS scavenging system, including hsp70, catalase, glutathione synthase, and MnSOD. Furthermore, to determine the hormetic mechanism underlying these phenotypic and molecular changes, we performed a genome-wide profiling in HN-exposed and control flies. Genes encoding chitin metabolism were highly up-regulated, which could possibly serve to scavenge free radicals. These results identify prenatal HN exposure as a potential hormetic factor that may improve longevity and healthspan by enhancing defense mechanisms in Drosophila.
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Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria

Satomi Miwa, Rafal Czapiewski, Tengfei Wan, Amy Bell, Kirsten N. Hill, Thomas von Zglinicki, Gabriele Saretzki,

https://doi.org/10.18632/aging.101089 pp 2551—2567

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Miwa S, Czapiewski R, Wan T, Bell A, Hill KN, von Zglinicki T, Saretzki G, . Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria. . 8:2551-2567. https://doi.org/10.18632/aging.101089

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                TY  - JOUR
                AU  - Miwa, Satomi 
                AU  - Czapiewski, Rafal 
                AU  - Wan, Tengfei 
                AU  - Bell, Amy 
                AU  - Hill, Kirsten N. 
                AU  - von Zglinicki, Thomas 
                AU  - Saretzki, Gabriele 
                TI  - Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101089
                DO  - 10.18632/aging.101089
                SP  - 2551
                EP  - 2567
                PY  - 
                AB  - Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.
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Empirical verification of evolutionary theories of aging

Pavlo Kyryakov, Alejandra Gomez-Perez, Anastasia Glebov, Nimara Asbah, Luigi Bruno, Carolynne Meunier, Tatiana Iouk, Vladimir I. Titorenko,

https://doi.org/10.18632/aging.101090 pp 2568—2589

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Kyryakov P, Gomez-Perez A, Glebov A, Asbah N, Bruno L, Meunier C, Iouk T, Titorenko VI, . Empirical verification of evolutionary theories of aging. . 8:2568-2589. https://doi.org/10.18632/aging.101090

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                TY  - JOUR
                AU  - Kyryakov, Pavlo 
                AU  - Gomez-Perez, Alejandra 
                AU  - Glebov, Anastasia 
                AU  - Asbah, Nimara 
                AU  - Bruno, Luigi 
                AU  - Meunier, Carolynne 
                AU  - Iouk, Tatiana 
                AU  - Titorenko, Vladimir I. 
                TI  - Empirical verification of evolutionary theories of aging
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101090
                DO  - 10.18632/aging.101090
                SP  - 2568
                EP  - 2589
                PY  - 
                AB  - We recently selected 3 long-lived mutant strains of Saccharomyces cerevisiae by a lasting exposure to exogenous lithocholic acid. Each mutant strain can maintain the extended chronological lifespan after numerous passages in medium without lithocholic acid. In this study, we used these long-lived yeast mutants for empirical verification of evolutionary theories of aging. We provide evidence that the dominant polygenic trait extending longevity of each of these mutants 1) does not affect such key features of early-life fitness as the exponential growth rate, efficacy of post-exponential growth and fecundity; and 2) enhances such features of early-life fitness as susceptibility to chronic exogenous stresses, and the resistance to apoptotic and liponecrotic forms of programmed cell death. These findings validate evolutionary theories of programmed aging. We also demonstrate that under laboratory conditions that imitate the process of natural selection within an ecosystem, each of these long-lived mutant strains is forced out of the ecosystem by the parental wild-type strain exhibiting shorter lifespan. We therefore concluded that yeast cells have evolved some mechanisms for limiting their lifespan upon reaching a certain chronological age. These mechanisms drive the evolution of yeast longevity towards maintaining a finite yeast chronological lifespan within ecosystems.
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Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice

Brian C. Grieb, Kelli Boyd, Ramkrishna Mitra, Christine M. Eischen,

https://doi.org/10.18632/aging.101092 pp 2590—2602

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Grieb BC, Boyd K, Mitra R, Eischen CM, . Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice. . 8:2590-2602. https://doi.org/10.18632/aging.101092

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                TY  - JOUR
                AU  - Grieb, Brian C. 
                AU  - Boyd, Kelli 
                AU  - Mitra, Ramkrishna 
                AU  - Eischen, Christine M. 
                TI  - Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice
                JO  - 
                JA  - 
                VL  - 8
                IS  - 10
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.101092
                DO  - 10.18632/aging.101092
                SP  - 2590
                EP  - 2602
                PY  - 
                AB  - Alterations of specific genes can modulate aging. Myc, a transcription factor that regulates the expression of many genes involved in critical cellular functions was shown to have a role in controlling longevity. Decreased expression of Myc inhibited many of the deleterious effects of aging and increased lifespan in mice. Without altering Myc expression, reduced levels of Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity and proliferation, while increased levels promote Myc-mediated effects. To determine the contribution of Mtbp to the effects of Myc on aging, we studied a large cohort of Mtbp heterozygous mice and littermate matched wild-type controls. Mtbp haploinsufficiency significantly increased longevity and maximal survival in mice. Reduced levels of Mtbp did not alter locomotor activity, litter size, or body size, but Mtbp heterozygous mice did exhibit elevated markers of metabolism, particularly in the liver. Mtbp+/- mice also had a significant delay in spontaneous cancer development, which was most prominent in the hematopoietic system, and an altered tumor spectrum compared to Mtbp+/+ mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that mimics some, but not all, of the properties of Myc in aging.
                ER  -

Volume 8, Issue 10

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Editorials

Simone Di Franco, Gianluca Sala, Matilde Todaro,

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Didier Decaudin, Christophe Le Tourneau,

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Sreenivasulu Chintala, Roberto Pili,

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Sergio Casas-Tintó, Marta Portela, Alberto Ferrús,

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Reviews

Bernard W. Perridon, Henri G.D. Leuvenink, Jan-Luuk Hillebrands, Harry van Goor, Eelke M. Bos,

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Munehiro Kitada, Yoshio Ogura, Daisuke Koya,

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Research Papers

Ganye Zhao, Hui Wang, Chenzhong Xu, Pan Wang, Jun Chen, Pengfeng Wang, Zhaomeng Sun, Yuanyuan Su, Zhao Wang, Limin Han, Tanjun Tong,

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Dahai Liu, Qiang Zhang, Hong Zhang, Ling Tang, Wei Li, Dongming Zhang, Guoying Wu, Shoudong Ye, Qian Ban, Kan He,

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Zhi-Yuan Li, Zhao-Li Chen, Ting Zhang, Chao Wei, Wei-Yun Shi,

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Daniela Volonte, Zhongmin Liu, Sruti Shiva, Ferruccio Galbiati,

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Kathleen E. Fischer, Jessica M. Hoffman, Lauren B. Sloane, Jonathan A.L. Gelfond, Vanessa Y. Soto, Arlan G. Richardson, Steven N. Austad,

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Joohwee Kim, Vivek Vaish, Mingxiao Feng, Kevin Field, Ioulia Chatzistamou, Minsub Shim,

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Yuji Shimizu, Shimpei Sato, Jun Koyamatsu, Hirotomo Yamanashi, Mako Nagayoshi, Koichiro Kadota, Takahiro Maeda,

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Leland Perice, Nir Barzilai, Joe Verghese, Erica F. Weiss, Roee Holtzer, Pinchas Cohen, Sofiya Milman,

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Amelia Pollard, Freya Shephard, James Freed, Susan Liddell, Lisa Chakrabarti,

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Karolina Piotrowicz, Agnieszka Pac, Anna Barbara Skalska, Jerzy Chudek, Alicja Klich-Rączka, Aleksandra Szybalska, Jean-Pierre Michel, Tomasz Grodzicki,

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Nadezhda V. Petrova, Artem V. Luzhin, Ekaterina O. Serebrovskaya, Alina P. Ryumina, Artem K. Velichko, Sergey V. Razin, Omar L. Kantidze,

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Thomas Broggini, Lisa Schnell, Ali Ghoochani, José María Mateos, Michael Buchfelder, Kurt Wiendieck, Michael K. Schäfer, Ilker Y. Eyupoglu, Nicolai E. Savaskan,

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Thomas Walker, Christos Michaelides, Antigoni Ekonomou, Kalotina Geraki, Harold G Parkes, Maria Suessmilch, Amy H Herlihy, William R Crum, Po-Wah So,

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