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NPJ Aging and Mechanisms of Disease

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https://www.readbyqxmd.com/read/30416740/ca1-nampt-knockdown-recapitulates-hippocampal-cognitive-phenotypes-in-old-mice-which-nicotinamide-mononucleotide-improves
#1
Sean Johnson, David F Wozniak, S Imai
Cognitive dysfunction is one of the most concerning outcomes in global population aging. However, the mechanisms by which cognitive functions are impaired during aging remain elusive. It has been established that NAD+ levels are reduced in multiple tissues and organs, including the brain. We found that NAD+ levels declined in the hippocampus of mice during the course of aging, and whereas we observed minimal age-related effects on spatial learning/memory capabilities in old mice, we discovered that they developed cognitive hypersensitivity in response to aversive stimulation during contextual fear conditioning tests...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/30181898/clampdown-of-inflammation-in-aging-and-anticancer-therapies-by-limiting-upregulation-and-activation-of-gpcr-cxcr4
#2
Raji R Nair, Shreyas V Madiwale, Deepak Kumar Saini
One of the major pathological outcomes of DNA damage during aging or anticancer therapy is enhanced inflammation. However, the underlying signaling mechanism that drives this is not well understood. Here, we show that in response to DNA damage, ubiquitously expressed GPCR, CXCR4 is upregulated through the ATM kinase-HIF1α dependent DNA damage response (DDR) signaling, and enhances inflammatory response when activated by its ligand, chemokine CXCL12. A pharmacologically active compound screen revealed that this increased inflammation is dependent on reduction in cAMP levels achieved through activation of Gαi through CXCR4 receptor and PDE4A...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/30155270/erratum-author-correction-repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#3
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
[This corrects the article DOI: 10.1038/s41514-017-0016-9.].
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29951223/the-annual-rate-of-coronary-artery-calcification-with-combination-therapy-with-a-pcsk9-inhibitor-and-a-statin-is-lower-than-that-with-statin-monotherapy
#4
Yuichi Ikegami, Ikuo Inoue, Kaiji Inoue, Yuichi Shinoda, Shinichiro Iida, Seiichi Goto, Takanari Nakano, Akira Shimada, Mistuhiko Noda
Statins and/or PCSK9 inhibitors cause the regression of coronary atheroma and reduce clinical events. However, it currently remains unclear whether these drugs modulate coronary atheroma calcification in vivo. Coronary artery calcium (CAC) scores (Agatston Units, AUs) were estimated in 120 patients receiving coronary computed tomographic angiography (CCTA) (63% males; median age 56 years). The CAC scores were compared among the three groups: (1) neither statin nor PCSK9 inhibitor therapy, (2) statin monotherapy, and (3) statin and PCSK9 inhibitor combination therapy in an unpaired cross-sectional study...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29928508/a-parthenogenetic-quasi-program-causes-teratoma-like-tumors-during-aging-in-wild-type-c-elegans
#5
Hongyuan Wang, Yuan Zhao, Marina Ezcurra, Alexandre Benedetto, Ann F Gilliat, Josephine Hellberg, Ziyu Ren, Evgeniy R Galimov, Trin Athigapanich, Johannes Girstmair, Maximilian J Telford, Colin T Dolphin, Zhizhou Zhang, David Gems
A long-standing belief is that aging (senescence) is the result of stochastic damage accumulation. Alternatively, senescent pathology may also result from late-life, wild-type gene action (i.e., antagonistic pleiotropy, as argued by Williams) leading to non-adaptive run-on of developmental programs (or quasi-programs ) (as suggested more recently by Blagosklonny). In this study, we use existing and new data to show how uterine tumors, a prominent form of senescent pathology in the nematode Caenorhabditis elegans , likely result from quasi-programs...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29675265/tissue-specific-transcriptome-profiling-of-drosophila-reveals-roles-for-gata-transcription-factors-in-longevity-by-dietary-restriction
#6
Adam J Dobson, Xiaoli He, Eric Blanc, Ekin Bolukbasi, Yodit Feseha, Mingyao Yang, Matthew D W Piper
Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29675264/blocking-negative-effects-of-senescence-in-human-skin-fibroblasts-with-a-plant-extract
#7
Ingo Lämmermann, Lucia Terlecki-Zaniewicz, Regina Weinmüllner, Markus Schosserer, Hanna Dellago, André Dargen de Matos Branco, Dominik Autheried, Benjamin Sevcnikar, Lisa Kleissl, Irina Berlin, Frédérique Morizot, Francois Lejeune, Nicola Fuzzati, Sandra Forestier, Alix Toribio, Anaïs Tromeur, Lionel Weinberg, Juan Carlos Higareda Almaraz, Marcel Scheideler, Marion Rietveld, Abdoel El Ghalbzouri, Erwin Tschachler, Florian Gruber, Johannes Grillari
There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29560271/natural-variation-of-chronological-aging-in-the-saccharomyces-cerevisiae-species-reveals-diet-dependent-mechanisms-of-life-span-control
#8
Paul P Jung, Zhi Zhang, Nicole Paczia, Christian Jaeger, Tomasz Ignac, Patrick May, Carole L Linster
Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae , mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29449960/physician-initiated-clinical-study-of-limb-ulcers-treated-with-a-functional-peptide-sr-0379-from-discovery-to-a-randomized-double-blind-placebo-controlled-trial
#9
Hironori Nakagami, Ken Sugimoto, Takahiro Ishikawa, Taku Fujimoto, Toshifumi Yamaoka, Misa Hayashi, Eiji Kiyohara, Hiroshi Ando, Yuta Terabe, Yoichi Takami, Koichi Yamamoto, Yasushi Takeya, Minoru Takemoto, Masaya Koshizaka, Tamotsu Ebihara, Ayumi Nakamura, Mitsunori Nishikawa, Xiang Jing Yao, Hideki Hanaoka, Ichiro Katayama, Koutaro Yokote, Hiromi Rakugi
SR-0379 is a functional peptide that has wound healing effect with anti-microbial action, making it an ideal drug to prevent infection. To evaluate the safety, efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A multi-center, double-blind, randomized clinical study was conducted from October 2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes or critical limb ischemia and (2) wound size <6 cm in diameter...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29285399/fighting-against-a-protean-enemy-immunosenescence-vaccines-and-healthy-aging
#10
Giuseppe Del Giudice, Jörg J Goronzy, Beatrix Grubeck-Loebenstein, Paul-Henri Lambert, Tomas Mrkvan, Jeffrey J Stoddard, T Mark Doherty
The progressive increase of the aged population worldwide mandates new strategies to ensure sustained health and well-being with age. The development of better and/or new vaccines against pathogens that affect older adults is one pivotal intervention in approaching this goal. However, the functional decline of various physiological systems, including the immune system, requires novel approaches to counteract immunosenescence. Although important progress has been made in understanding the mechanisms underlying the age-related decline of the immune response to infections and vaccinations, knowledge gaps remain, both in the areas of basic and translational research...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29214052/neuroprotective-role-of-retinal-sirt3-against-acute-photo-stress
#11
Norimitsu Ban, Yoko Ozawa, Hideto Osada, Jonathan B Lin, Eriko Toda, Mitsuhiro Watanabe, Kenya Yuki, Shunsuke Kubota, Rajendra S Apte, Kazuo Tsubota
SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29214051/cytochrome-b5-protects-photoreceptors-from-light-stress-induced-lipid-peroxidation-and-retinal-degeneration
#12
Xinping Chen, Hana Hall, Jeffrey P Simpson, Walter D Leon-Salas, Donald F Ready, Vikki M Weake
Lipid peroxides are generated by oxidative stress in cells, and contribute to ageing and neurodegenerative disease. The eye is at special risk for lipid peroxidation because photoreceptors possess amplified sensory membranes rich in peroxidation-susceptible polyunsaturated fatty acids. Light-induced lipid peroxidation in the retina contributes to retinal degeneration, and lipid peroxidation has been implicated in the progression of age-associated ocular diseases such as age-related macular degeneration (AMD)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29184669/repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#13
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29167747/health-benefits-of-late-onset-metformin-treatment-every-other-week-in-mice
#14
Irene Alfaras, Sarah J Mitchell, Hector Mora, Darisbeth Rosario Lugo, Alessandra Warren, Ignacio Navas-Enamorado, Vickie Hoffmann, Christopher Hine, James R Mitchell, David G Le Couteur, Victoria C Cogger, Michel Bernier, Rafael de Cabo
Chronic 1% metformin treatment is nephrotoxic in mice, but this dose may nonetheless confer health benefits if given intermittently rather than continuously. Here, we examined the effects of 1% metformin given every-other week (EOW) or two consecutive weeks per month (2WM) on survival of 2-year-old male mice fed standard chow. EOW and 2WM mice had comparable life span compared with control mice. A significant reduction in body weight within the first few weeks of metformin treatment was observed without impact on food consumption and energy expenditure...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29134111/periodontitis-induced-by-bacterial-infection-exacerbates-features-of-alzheimer-s-disease-in-transgenic-mice
#15
Naoyuki Ishida, Yuichi Ishihara, Kazuto Ishida, Hiroyuki Tada, Yoshiko Funaki-Kato, Makoto Hagiwara, Taslima Ferdous, Mohammad Abdullah, Akio Mitani, Makoto Michikawa, Kenji Matsushita
Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis . Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29134110/erratum-ubiquitous-overexpression-of-the-dna-repair-factor-dprp19-reduces-dna-damage-and-extends-drosophila-life-span
#16
Kathrin Garschall, Hanna Dellago, Martina Gáliková, Markus Schosserer, Thomas Flatt, Johannes Grillari
[This corrects the article DOI: 10.1038/s41514-017-0005-z.].
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28970944/somatic-growth-aging-and-longevity
#17
REVIEW
Andrzej Bartke
Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various "pro-aging" effects...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28944077/how-does-hormesis-impact-biology-toxicology-and-medicine
#18
REVIEW
Edward J Calabrese, Mark P Mattson
Hormesis refers to adaptive responses of biological systems to moderate environmental or self-imposed challenges through which the system improves its functionality and/or tolerance to more severe challenges. The past two decades have witnessed an expanding recognition of the concept of hormesis, elucidation of its evolutionary foundations, and underlying cellular and molecular mechanisms, and practical applications to improve quality of life. To better inform future basic and applied research, we organized and re-evaluated recent hormesis-related findings with the intent of incorporating new knowledge of biological mechanisms, and providing fundamental insights into the biological, biomedical and risk assessment implications of hormesis...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28900540/treatment-of-diabetic-mice-with-the-sglt2-inhibitor-ta-1887-antagonizes-diabetic-cachexia-and-decreases-mortality
#19
Taichi Sugizaki, Shunshun Zhu, Ge Guo, Akiko Matsumoto, Jiabin Zhao, Motoyoshi Endo, Haruki Horiguchi, Jun Morinaga, Zhe Tian, Tsuyoshi Kadomatsu, Keishi Miyata, Hiroshi Itoh, Yuichi Oike
A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic db/db mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28868154/smarcd1-regulates-senescence-associated-lipid-accumulation-in-hepatocytes
#20
Chisato Inoue, Chong Zhao, Yumi Tsuduki, Miyako Udono, Lixiang Wang, Masatoshi Nomura, Yoshinori Katakura
Previously, we have identified 16 senescence-associated genes by a subtractive proteomic analysis using presenescent and senescent human fibroblast cells, TIG-1. The aim of this study was to clarify the role of SMARCD1, one of the identified genes, also known as BAF60a, in hepatic senescence. SMARCD1 is a member of the SWI/SNF chromatin remodeling complex family, and regulates the transcription of target genes through the alterations of chromatin structure. We demonstrated that the reduced expression of SMARCD1 triggers cellular senescence and induces the accumulation of lipids, suggesting that SMARCD1 acts as a mediator in these processes...
2017: NPJ Aging and Mechanisms of Disease
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