Volume 5, Issue 7

Rejuvenating nerve cells in adults

Hui Chiu, Chieh Chang,

https://doi.org/10.18632/aging.100574 pp 485—486

PDF How to Cite Request Reprint

Cite this Article

How to cite

Chiu H, Chang C, . Rejuvenating nerve cells in adults. . 5:485-486. https://doi.org/10.18632/aging.100574

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Click to copy this citation from the text box above or download the citation:

Multifaceted aging and rapamycin

Vladimir N. Anisimov,

https://doi.org/10.18632/aging.100575 pp 487

PDF How to Cite Request Reprint

p53 and aging: role of p66Shc

Enrica Migliaccio, Marco Giorgio, Pier Giuseppe Pelicci,

https://doi.org/10.18632/aging.100583 pp 488—489

PDF How to Cite Request Reprint

M(o)TOR of aging: MTOR as a universal molecular hypothalamus

Mikhail V. Blagosklonny,

https://doi.org/10.18632/aging.100580 pp 490—494

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Blagosklonny MV, . M(o)TOR of aging: MTOR as a universal molecular hypothalamus. . 5:490-494. https://doi.org/10.18632/aging.100580

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Blagosklonny, Mikhail V. 
                TI  - M(o)TOR of aging: MTOR as a universal molecular hypothalamus
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100580
                DO  - 10.18632/aging.100580
                SP  - 490
                EP  - 494
                PY  - 
                AB  - A recent ground-breaking publication described hypothalamus-driven programmatic aging. As a Russian proverb goes “everything new is well-forgotten old”. In 1958, Dilman proposed that aging and its related diseases are programmed by the hypothalamus. This theory, supported by beautiful experiments, remained unnoticed just to be re-discovered recently. Yet, it does not explain all manifestations of aging. And would organism age without hypothalamus? Do sensing pathways such as MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a “molecular hypothalamus” in every cell? Are hypothalamus-driven alterations simply a part of quasi-programmed aging manifested by hyperfunction and secondary signal-resistance? Here are some answers.
                ER  -

Click to copy this citation from the text box above or download the citation:

A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations

James M. Smoliga, E. Sage Colombo, Matthew J. Campen,

https://doi.org/10.18632/aging.100579 pp 495—506

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Smoliga JM, Colombo ES, Campen MJ, . A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations. . 5:495-506. https://doi.org/10.18632/aging.100579

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Smoliga, James M. 
                AU  - Colombo, E. Sage 
                AU  - Campen, Matthew J. 
                TI  - A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100579
                DO  - 10.18632/aging.100579
                SP  - 495
                EP  - 506
                PY  - 
                AB  - In recent years, the wealth of basic science research supporting resveratrol's potential to treat, delay, and even prevent age-related chronic diseases has led to a number of human clinical trials. While such translational research has yielded promising results in clinical populations, recently published conflicting results from studies evaluating resveratrol's potential for primary prevention of chronic disease in healthy / asymptomatic individuals have generated considerable controversy and do not initially appear consistent with findings from animal models. We argue that trials targeting healthy humans are often fundamentally flawed owing to inappropriate use of paradigms only applicable to populations with overt clinical disease and the consequent misleading (typically negative) results can severely retard advancement of drug development. To appropriately perform translational research centered on resveratrol as a primary prevention agent in non-clinical populations, it is critical to utilize study designs which can provide adequate information on clinically relevant outcome measures, avoid paradigms and assumptions from interventions which are specific to clinical populations, and maintain realistic expectations compared to interventions which provide the theoretical maximal response (e.g., caloric restriction and aerobic exercise training).
                ER  -

Click to copy this citation from the text box above or download the citation:

Will calorie restriction work in humans?

Edda Cava, Luigi Fontana,

https://doi.org/10.18632/aging.100581 pp 507—514

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Cava E, Fontana L, . Will calorie restriction work in humans?. . 5:507-514. https://doi.org/10.18632/aging.100581

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Cava, Edda 
                AU  - Fontana, Luigi 
                TI  - Will calorie restriction work in humans?
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100581
                DO  - 10.18632/aging.100581
                SP  - 507
                EP  - 514
                PY  - 
                AB  - Calorie Restriction (CR) without malnutrition slows aging and increases average and maximal lifespan in simple model organisms and rodents. In rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, so far CR significantly increased average lifespan only in the Wisconsin, but not in the NIA monkey study. Differences in diet composition and study design between the 2 on-going trials may explain the discrepancies in survival and disease. Nevertheless, many of the metabolic and hormonal adaptations that are typical of the long-lived CR rodents did not occur in either the NIA or WNPRC CR monkeys. Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer. Moreover, CR in human beings improves markers of cardiovascular aging, and rejuvenates the skeletal muscle transcriptional profile. More studies are needed to understand the interactions between CR, diet composition, exercise, and other environmental and psychological factors on metabolic and molecular pathways that regulate health and longevity.
                ER  -

Click to copy this citation from the text box above or download the citation:

Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK

Ehtesham Shafique, Wing C. Choy, Yuhong Liu, Jun Feng, Brenda Cordeiro, Arthur Lyra, Mohammed Arafah, Abdulmounem Yassin-Kassab, Arthus V.D. Zanetti, Richard T. Clements, Cesario Bianchi, Laura E. Benjamin, Frank W. Sellke, Md. Ruhul Abid,

https://doi.org/10.18632/aging.100569 pp 515—530

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Shafique E, Choy WC, Liu Y, Feng J, Cordeiro B, Lyra A, Arafah M, Yassin-Kassab A, Zanetti AV, Clements RT, Bianchi C, Benjamin LE, Sellke FW, et al, . Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK. . 5:515-530. https://doi.org/10.18632/aging.100569

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Shafique, Ehtesham 
                AU  - Choy, Wing C. 
                AU  - Liu, Yuhong 
                AU  - Feng, Jun 
                AU  - Cordeiro, Brenda 
                AU  - Lyra, Arthur 
                AU  - Arafah, Mohammed 
                AU  - Yassin-Kassab, Abdulmounem 
                AU  - Zanetti, Arthus V.D. 
                AU  - Clements, Richard T. 
                AU  - Bianchi, Cesario 
                AU  - Benjamin, Laura E. 
                AU  - Sellke, Frank W. 
                AU  - Abid, Md. Ruhul 
                TI  - Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100569
                DO  - 10.18632/aging.100569
                SP  - 515
                EP  - 530
                PY  - 
                ER  -

Provider: 
                TY  - JOUR
                AU  - Shafique, Ehtesham 
                AU  - Choy, Wing C. 
                AU  - Liu, Yuhong 
                AU  - Feng, Jun 
                AU  - Cordeiro, Brenda 
                AU  - Lyra, Arthur 
                AU  - Arafah, Mohammed 
                AU  - Yassin-Kassab, Abdulmounem 
                AU  - Zanetti, Arthus V.D. 
                AU  - Clements, Richard T. 
                AU  - Bianchi, Cesario 
                AU  - Benjamin, Laura E. 
                AU  - Sellke, Frank W. 
                AU  - Abid, Md. Ruhul 
                TI  - Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100569
                DO  - 10.18632/aging.100569
                SP  - 515
                EP  - 530
                PY  - 
                AB  - Age-associated decline in cardiovascular function is believed to occur from the deleterious effects of reactive oxygen species (ROS). However, failure of recent clinical trials using antioxidants in patients with cardiovascular disease, and the recent findings showing paradoxical role for NADPH oxidase-derived ROS in endothelial function challenge this long-held notion against ROS. Here, we examine the effects of endothelium-specific conditional increase in ROS on coronary endothelial function. We have generated a novel binary (Tet-ON/OFF) conditional transgenic mouse (Tet-Nox2:VE-Cad-tTA) that induces endothelial cell (EC)-specific overexpression of Nox2/gp91 (NADPH oxidase) and 1.8±0.42-fold increase in EC-ROS upon tetracycline withdrawal (Tet-OFF). We examined ROS effects on EC signaling and function. First, we demonstrate that endothelium-dependent coronary vasodilation was significantly improved in Tet-OFF Nox2 compared to Tet-ON (control) littermates. Using EC isolated from mouse heart, we show that endogenous ROS increased eNOS activation and nitric oxide (NO) synthesis through activation of the survival kinase AMPK. Coronary vasodilation in Tet-OFF Nox2 animals was CaMKKβ-AMPK-dependent. Finally, we demonstrate that AMPK activation induced autophagy and thus, protected ECs from oxidant-induced cell death. Together, these findings suggest that increased ROS levels, often associated with cardiovascular conditions in advanced age, play a protective role in endothelial homeostasis by inducing AMPK-eNOS axis.
                ER  -

Click to copy this citation from the text box above or download the citation:

Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts

David Vindrieux, Baptiste Gras, Merce Garcia-Belinchon, Samia Mourah, Céleste Lebbe, Arnaud Augert, David Bernard,

https://doi.org/10.18632/aging.100577 pp 531—538

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Vindrieux D, Gras B, Garcia-Belinchon M, Mourah S, Lebbe C, Augert A, Bernard D, . Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts. . 5:531-538. https://doi.org/10.18632/aging.100577

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Vindrieux, David 
                AU  - Gras, Baptiste 
                AU  - Garcia-Belinchon, Merce 
                AU  - Mourah, Samia 
                AU  - Lebbe, Céleste 
                AU  - Augert, Arnaud 
                AU  - Bernard, David 
                TI  - Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100577
                DO  - 10.18632/aging.100577
                SP  - 531
                EP  - 538
                PY  - 
                AB  - Normal cells enter a senescent state upon aberrant oncogenic signals and this response inhibits tumor initiation and progression. It is now well admitted that intracellular and membrane localized oncogenes can illicit oncogene induced senescence. However, the effect of mitogenic growth factor on cellular senescence is so far largely unknown. Here we show that normal human dermal fibroblasts display a complex response to Platelet derived growth factor B (PDGFB) expression. Indeed, PDGFB expression induces, in the same cell population, both senescence and cellular transformation. Remarkably both populations are sustained with passages suggesting that transformed cells eventually enter a senescent state. This senescence state is p53 dependent as inhibiting the p53 pathway blocks the ability of PDGFB to induce senescence and results in strong cellular transformation increase upon PDGFB expression. The relevance of these observations is supported by the fact that human dermatofibrosarcoma protuberans, skin tumors arising from constitutive PDGFB production with little aggressiveness, also display some senescence hallmarks. Together these data support the view that PDGFB, a mitogenic growth factor, has a limited ability to induce senescence. We propose that this low level of senescence might decrease the transforming ability of this factor without totally abolishing it.
                ER  -

Click to copy this citation from the text box above or download the citation:

Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

Lan Ye, Anne L. Widlund, Carrie A. Sims, Dudley W. Lamming, Yuxia Guan, James G. Davis, David M. Sabatini, David E. Harrison, Ole Vang, Joseph A. Baur,

https://doi.org/10.18632/aging.100576 pp 539—550

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Ye L, Widlund AL, Sims CA, Lamming DW, Guan Y, Davis JG, Sabatini DM, Harrison DE, Vang O, Baur JA, . Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance. . 5:539-550. https://doi.org/10.18632/aging.100576

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Ye, Lan 
                AU  - Widlund, Anne L. 
                AU  - Sims, Carrie A. 
                AU  - Lamming, Dudley W. 
                AU  - Guan, Yuxia 
                AU  - Davis, James G. 
                AU  - Sabatini, David M. 
                AU  - Harrison, David E. 
                AU  - Vang, Ole 
                AU  - Baur, Joseph A. 
                TI  - Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100576
                DO  - 10.18632/aging.100576
                SP  - 539
                EP  - 550
                PY  - 
                AB  - Rapamycin extends lifespan in mice, but can have a number of undesirable effects that may ultimately limit its utility in humans. The canonical target of rapamycin, and the one thought to account for its effects on lifespan, is the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). We have previously shown that at least some of the detrimental side effects of rapamycin are due to “off target” disruption of mTORC2, suggesting they could be avoided by more specific targeting of mTORC1. However, mTORC1 inhibition per se can reduce the mRNA expression of mitochondrial genes and compromise the function of mitochondria in cultured muscle cells, implying that defects in bioenergetics might be an unavoidable consequence of targeting mTORC1 in vivo. Therefore, we tested whether rapamycin, at the same doses used to extend lifespan, affects mitochondrial function in skeletal muscle. While mitochondrial transcripts were decreased, particularly in the highly oxidative soleus muscle, we found no consistent change in mitochondrial DNA or protein levels. In agreement with the lack of change in mitochondrial components, rapamycin-treated mice had endurance equivalent to that of untreated controls, and isolated, permeabilized muscle fibers displayed similar rates of oxygen consumption. We conclude that the doses of rapamycin required to extend life do not cause overt mitochondrial dysfunction in skeletal muscle.
                ER  -

Click to copy this citation from the text box above or download the citation:

Mitochondrial membrane lipidome defines yeast longevity

Adam Beach, Vincent R. Richard, Anna Leonov, Michelle T. Burstein, Simon D. Bourque, Olivia Koupaki, Mylène Juneau, Rachel Feldman, Tatiana Iouk, Vladimir I. Titorenko,

https://doi.org/10.18632/aging.100578 pp 551—574

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

Beach A, Richard VR, Leonov A, Burstein MT, Bourque SD, Koupaki O, Juneau M, Feldman R, Iouk T, Titorenko VI, . Mitochondrial membrane lipidome defines yeast longevity. . 5:551-574. https://doi.org/10.18632/aging.100578

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - Beach, Adam 
                AU  - Richard, Vincent R. 
                AU  - Leonov, Anna 
                AU  - Burstein, Michelle T. 
                AU  - Bourque, Simon D. 
                AU  - Koupaki, Olivia 
                AU  - Juneau, Mylène 
                AU  - Feldman, Rachel 
                AU  - Iouk, Tatiana 
                AU  - Titorenko, Vladimir I. 
                TI  - Mitochondrial membrane lipidome defines yeast longevity
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100578
                DO  - 10.18632/aging.100578
                SP  - 551
                EP  - 574
                PY  - 
                AB  - Our studies revealed that lithocholic acid (LCA), a bile acid, is a potent anti-aging natural compound that in yeast cultured under longevity-extending caloric restriction (CR) conditions acts in synergy with CR to enable a significant further increase in chronological lifespan. Here, we investigate a mechanism underlying this robust longevity-extending effect of LCA under CR. We found that exogenously added LCA enters yeast cells, is sorted to mitochondria, resides mainly in the inner mitochondrial membrane, and also associates with the outer mitochondrial membrane. LCA elicits an age-related remodeling of glycerophospholipid synthesis and movement within both mitochondrial membranes, thereby causing substantial changes in mitochondrial membrane lipidome and triggering major changes in mitochondrial size, number and morphology. In synergy, these changes in the membrane lipidome and morphology of mitochondria alter the age-related chronology of mitochondrial respiration, membrane potential, ATP synthesis and reactive oxygen species homeostasis. The LCA-driven alterations in the age-related dynamics of these vital mitochondrial processes extend yeast longevity. In sum, our findings suggest a mechanism underlying the ability of LCA to delay chronological aging in yeast by accumulating in both mitochondrial membranes and altering their glycerophospholipid compositions. We concluded that mitochondrial membrane lipidome plays an essential role in defining yeast longevity.
                ER  -

Click to copy this citation from the text box above or download the citation:

Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age

Grineva EN, Karonova T, Micheeva E, Belyaeva O, Belyaeva IL,

https://doi.org/10.18632/aging.100582 pp 575—581

View Abstract PDF Full-Text How to Cite Request Reprint

Cite this Article

How to cite

EN G, T K, E M, O B, IL B, . Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age. . 5:575-581. https://doi.org/10.18632/aging.100582

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
                TY  - JOUR
                AU  - EN, Grineva 
                AU  - T, Karonova 
                AU  - E, Micheeva 
                AU  - O, Belyaeva 
                AU  - IL, Belyaeva 
                TI  - Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age
                JO  - 
                JA  - 
                VL  - 5
                IS  - 7
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100582
                DO  - 10.18632/aging.100582
                SP  - 575
                EP  - 581
                PY  - 
                AB  - It was suggested that glucose metabolism and body fat content depend on serum levels of 25-hydroxyvitamin D [25(OH)D]. We studied 320 healthy women at late reproductive age of 40 to 52 years old (mean age 46.1±4.5) from St. Petersburg (North-West region of Russia). 25(OH)D levels were from 19.4 to 134.0 nMol/L (mean 52.9±22.7). Vitamin D deficiency (lower than 50 nMol/L) and insufficiency (50-75 nMol/L) was revealed in 59.1% and 27.8% of women, respectively. The study showed that low 25(OH)D levels were associated with obesity (r=-0.35, p&lt;0.01), increased plasma glucose levels after OGTT (r=-0.31, p&lt;0.01) and decreased insulin sensitivity index (r=-0.28, p&lt;0.01). We found that 25(OH)D levels below 50 nMol/L were associated with obesity risk (OR 2.25[1.05-3.95], CI 95%) but not with risk of impaired glucose metabolism (1.07[0.54-2.12],CI95%). Our results showed that vitamin D insufficiency is highly prevalent in the population of healthy women. Low 25(OH)D levels correlated with high body fat, glucose levels and decreased insulin sensitivity. We conclude that vitamin D deficiency is a potential risk factor for obesity and development of insulin resistance leading to diabetes type 2.
                ER  -

Click to copy this citation from the text box above or download the citation:

Volume 5, Issue 7

Editorials

Rejuvenating nerve cells in adults

Hui Chiu, Chieh Chang,

Multifaceted aging and rapamycin

Vladimir N. Anisimov,

p53 and aging: role of p66Shc

Enrica Migliaccio, Marco Giorgio, Pier Giuseppe Pelicci,

Research Perspectives

M(o)TOR of aging: MTOR as a universal molecular hypothalamus

Mikhail V. Blagosklonny,

A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations

James M. Smoliga, E. Sage Colombo, Matthew J. Campen,

Will calorie restriction work in humans?

Edda Cava, Luigi Fontana,

Research Papers

Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK

Ehtesham Shafique, Wing C. Choy, Yuhong Liu, Jun Feng, Brenda Cordeiro, Arthur Lyra, Mohammed Arafah, Abdulmounem Yassin-Kassab, Arthus V.D. Zanetti, Richard T. Clements, Cesario Bianchi, Laura E. Benjamin, Frank W. Sellke, Md. Ruhul Abid,

Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts

David Vindrieux, Baptiste Gras, Merce Garcia-Belinchon, Samia Mourah, Céleste Lebbe, Arnaud Augert, David Bernard,

Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

Lan Ye, Anne L. Widlund, Carrie A. Sims, Dudley W. Lamming, Yuxia Guan, James G. Davis, David M. Sabatini, David E. Harrison, Ole Vang, Joseph A. Baur,

Mitochondrial membrane lipidome defines yeast longevity

Adam Beach, Vincent R. Richard, Anna Leonov, Michelle T. Burstein, Simon D. Bourque, Olivia Koupaki, Mylène Juneau, Rachel Feldman, Tatiana Iouk, Vladimir I. Titorenko,

Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age

Grineva EN, Karonova T, Micheeva E, Belyaeva O, Belyaeva IL,

Explore This Issue