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https://www.readbyqxmd.com/read/29107505/system-wide-benefits-of-intermeal-fasting-by-autophagy
#1
Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E Pessin, Gary J Schwartz, Sander Kersten, Rajat Singh
Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin...
October 24, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29050682/effect-of-exceptional-parental-longevity-and-lifestyle-factors-on-prevalence-of-cardiovascular-disease-in-offspring
#2
Sriram Gubbi, Elianna Schwartz, Jill Crandall, Joe Verghese, Roee Holtzer, Gil Atzmon, Rebecca Braunstein, Nir Barzilai, Sofiya Milman
Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence of cardiovascular disease (CVD), but the role of lifestyle factors in this unique cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD independent of lifestyle factors. Prevalence of CVD and CVD risk factors was assessed in a population of community-dwelling Ashkenazi Jewish adults aged 65 to 94 years. Participants included OPEL (n = 395), defined as having at least 1 parent living past the age of 95 years, and offspring of parents with usual survival (OPUS, n = 450), defined as having neither parent survive to 95 years...
September 18, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28982655/erratum-mediobasal-hypothalamic-sirt1-is-essential-for-resveratrol-s-effects-on-insulin-action-in-rats-diabetes-2011-60-2691-2700
#3
Colette M Knight, Roger Gutierrez-Juarez, Tony K T Lam, Isabel Arrieta-Cruz, Loli Huang, Gary Schwartz, Nir Barzilai, Luciano Rossetti
No abstract text is available yet for this article.
October 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28977569/effects-of-foxo3-polymorphisms-on-survival-to-extreme-longevity-in-four-centenarian-studies
#4
Harold Bae, Anastasia Gurinovich, Alberto Malovini, Gil Atzmon, Stacy L Andersen, Francesco Villa, Nir Barzilai, Annibale Puca, Thomas T Perls, Paola Sebastiani
Previous studies note specific FOXO3 single-nucleotide polymorphisms (SNPs) associated with human longevity. However, it is not clear if these SNPs influence mortality risk beyond the oldest 1 percentile of survival. Using data from four longevity studies (total n = 8,266, age range 96-119 years for cases), we tested gene-wide association between 107 SNPs and survival to at least the oldest 1 percentile of survival for the 1900 birth cohort (≥96, white males; ≥100 white females). This analysis replicated 17 previously published variants, several of which are significant expression quantitative trait loci of FOXO3; rs6911407 and rs2253310 have the most significant effect on FOXO3 expressions in brain tissue...
July 18, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28705468/association-of-anti-inflammatory-cytokine-il10-polymorphisms-with-motoric-cognitive-risk-syndrome-in-an-ashkenazi-jewish-population
#5
Sanish Sathyan, Nir Barzilai, Gil Atzmon, Sofiya Milman, Emmeline Ayers, Joe Verghese
Motoric cognitive risk (MCR) syndrome is a newly described predementia syndrome characterized by the presence of cognitive complaints and slow gait, which is associated with increased risk of conversion to dementia. The underlying biological mechanisms for MCR have not yet been established. Neuroinflammation mediated through cytokines plays a pivotal role in the pathogenesis of dementia. Hence, our objective was to prospectively examine whether variations in cytokine genes (CRP, IFNG, IL1A, IL1B, IL4, IL6, IL10, IL18, TNF, and IL12A) play a role in MCR incidence in 530 community-dwelling Ashkenazi Jewish adults aged 65 years and older without MCR or dementia at baseline enrolled in the LonGenity study...
October 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28630896/the-gh-receptor-exon-3-deletion-is-a-marker-of-male-specific-exceptional-longevity-associated-with-increased-gh-sensitivity-and-taller-stature
#6
Danny Ben-Avraham, Diddahally R Govindaraju, Temuri Budagov, Delphine Fradin, Peter Durda, Bing Liu, Sandy Ott, Danielle Gutman, Lital Sharvit, Robert Kaplan, Pierre Bougnères, Alex Reiner, Alan R Shuldiner, Pinchas Cohen, Nir Barzilai, Gil Atzmon
Although both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling were shown to regulate life span in lower organisms, the role of GH signaling in human longevity remains unclear. Because a GH receptor exon 3 deletion (d3-GHR) appears to modulate GH sensitivity in humans, we hypothesized that this polymorphism could play a role in human longevity. We report a linear increased prevalence of d3-GHR homozygosity with age in four independent cohorts of long-lived individuals: 841 participants [567 of the Longevity Genes Project (LGP) (8% increase; P = 0...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28592838/the-first-neanderthal-remains-from-an-open-air-middle-palaeolithic-site-in-the-levant
#7
Ella Been, Erella Hovers, Ravid Ekshtain, Ariel Malinski-Buller, Nuha Agha, Alon Barash, Daniella E Bar-Yosef Mayer, Stefano Benazzi, Jean-Jacques Hublin, Lihi Levin, Noam Greenbaum, Netta Mitki, Gregorio Oxilia, Naomi Porat, Joel Roskin, Michalle Soudack, Reuven Yeshurun, Ruth Shahack-Gross, Nadav Nir, Mareike C Stahlschmidt, Yoel Rak, Omry Barzilai
The late Middle Palaeolithic (MP) settlement patterns in the Levant included the repeated use of caves and open landscape sites. The fossil record shows that two types of hominins occupied the region during this period-Neandertals and Homo sapiens. Until recently, diagnostic fossil remains were found only at cave sites. Because the two populations in this region left similar material cultural remains, it was impossible to attribute any open-air site to either species. In this study, we present newly discovered fossil remains from intact archaeological layers of the open-air site 'Ein Qashish, in northern Israel...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486590/activation-induced-autophagy-is-preserved-in-cd4-t-cells-in-familial-longevity
#8
Yotam Raz, Ignacio Guerrero-Ros, Andrea Maier, P Eline Slagboom, Gil Atzmon, Nir Barzilai, Fernando Macian
As with many other tissues and organs, the immune system is also affected by age. Immunosenescence is characterized by a decreased ability of immune cells to mount a productive response upon exposure to new antigens. Several studies have reported that members of families with exceptional longevity show improved immune function, which might contribute to the increased life- and health-span observed in those families. Autophagy is a catabolic process that delivers cytoplasmic material to the lysosomes for degradation...
September 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28406265/symptoms-of-apathy-independently-predict-incident-frailty-and-disability-in-community-dwelling-older-adults
#9
Emmeline Ayers, Miriam Shapiro, Roee Holtzer, Nir Barzilai, Sofiya Milman, Joe Verghese
OBJECTIVE: Although depressive symptoms are widely recognized as a predictor of functional decline among older adults, little is known about the predictive utility of apathy in this population. We prospectively examined apathy symptoms as predictors of incident slow gait, frailty, and disability among non-demented, community-dwelling older adults. METHODS: We examined 2 independent prospective cohort studies-the LonGenity study (N = 625, 53% women, mean age = 75...
May 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28379407/association-of-family-history-of-exceptional-longevity-with-decline-in-physical-function-in-aging
#10
Emmeline Ayers, Nir Barzilai, Jill P Crandall, Sofiya Milman, Joe Verghese
Background: Although many genetic and nongenetic factors interact to determine an individual's physical phenotype, there has been limited examination of the contribution of family history of exceptional parental longevity on decline in physical function in aging. Methods: The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish adults age 65 and older, who were defined as either offspring of parents with exceptional longevity ([OPEL]: having at least one parent who lived to age 95 or older) or offspring of parents with usual survival ([OPUS]: neither parent survived to age 95)...
November 9, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28364543/clinical-trials-targeting-aging-and-age-related-multimorbidity
#11
Mark A Espeland, Eileen M Crimmins, Brandon R Grossardt, Jill P Crandall, Jonathan A L Gelfond, Tamara B Harris, Stephen B Kritchevsky, JoAnn E Manson, Jennifer G Robinson, Walter A Rocca, Marinella Temprosa, Fridtjof Thomas, Robert Wallace, Nir Barzilai
Background: There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods: Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results: Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging...
March 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28341696/a-low-frequency-inactivating-akt2-variant-enriched-in-the-finnish-population-is-associated-with-fasting-insulin-levels-and-type-2-diabetes-risk
#12
Alisa Manning, Heather M Highland, Jessica Gasser, Xueling Sim, Taru Tukiainen, Pierre Fontanillas, Niels Grarup, Manuel A Rivas, Anubha Mahajan, Adam E Locke, Pablo Cingolani, Tune H Pers, Ana Viñuela, Andrew A Brown, Ying Wu, Jason Flannick, Christian Fuchsberger, Eric R Gamazon, Kyle J Gaulton, Hae Kyung Im, Tanya M Teslovich, Thomas W Blackwell, Jette Bork-Jensen, Noël P Burtt, Yuhui Chen, Todd Green, Christopher Hartl, Hyun Min Kang, Ashish Kumar, Claes Ladenvall, Clement Ma, Loukas Moutsianas, Richard D Pearson, John R B Perry, N William Rayner, Neil R Robertson, Laura J Scott, Martijn van de Bunt, Johan G Eriksson, Antti Jula, Seppo Koskinen, Terho Lehtimäki, Aarno Palotie, Olli T Raitakari, Suzanne B R Jacobs, Jennifer Wessel, Audrey Y Chu, Robert A Scott, Mark O Goodarzi, Christine Blancher, Gemma Buck, David Buck, Peter S Chines, Stacey Gabriel, Anette P Gjesing, Christopher J Groves, Mette Hollensted, Jeroen R Huyghe, Anne U Jackson, Goo Jun, Johanne Marie Justesen, Massimo Mangino, Jacquelyn Murphy, Matt Neville, Robert Onofrio, Kerrin S Small, Heather M Stringham, Joseph Trakalo, Eric Banks, Jason Carey, Mauricio O Carneiro, Mark DePristo, Yossi Farjoun, Timothy Fennell, Jacqueline I Goldstein, George Grant, Martin Hrabé de Angelis, Jared Maguire, Benjamin M Neale, Ryan Poplin, Shaun Purcell, Thomas Schwarzmayr, Khalid Shakir, Joshua D Smith, Tim M Strom, Thomas Wieland, Jaana Lindstrom, Ivan Brandslund, Cramer Christensen, Gabriela L Surdulescu, Timo A Lakka, Alex S F Doney, Peter Nilsson, Nicholas J Wareham, Claudia Langenberg, Tibor V Varga, Paul W Franks, Olov Rolandsson, Anders H Rosengren, Vidya S Farook, Farook Thameem, Sobha Puppala, Satish Kumar, Donna M Lehman, Christopher P Jenkinson, Joanne E Curran, Daniel Esten Hale, Sharon P Fowler, Rector Arya, Ralph A DeFronzo, Hanna E Abboud, Ann-Christine Syvänen, Pamela J Hicks, Nicholette D Palmer, Maggie C Y Ng, Donald W Bowden, Barry I Freedman, Tõnu Esko, Reedik Mägi, Lili Milani, Evelin Mihailov, Andres Metspalu, Narisu Narisu, Leena Kinnunen, Lori L Bonnycastle, Amy Swift, Dorota Pasko, Andrew R Wood, João Fadista, Toni I Pollin, Nir Barzilai, Gil Atzmon, Benjamin Glaser, Barbara Thorand, Konstantin Strauch, Annette Peters, Michael Roden, Martina Müller-Nurasyid, Liming Liang, Jennifer Kriebel, Thomas Illig, Harald Grallert, Christian Gieger, Christa Meisinger, Lars Lannfelt, Solomon K Musani, Michael Griswold, Herman A Taylor, Gregory Wilson, Adolfo Correa, Heikki Oksa, William R Scott, Uzma Afzal, Sian-Tsung Tan, Marie Loh, John C Chambers, Jobanpreet Sehmi, Jaspal Singh Kooner, Benjamin Lehne, Yoon Shin Cho, Jong-Young Lee, Bok-Ghee Han, Annemari Käräjämäki, Qibin Qi, Lu Qi, Jinyan Huang, Frank B Hu, Olle Melander, Marju Orho-Melander, Jennifer E Below, David Aguilar, Tien Yin Wong, Jianjun Liu, Chiea-Chuen Khor, Kee Seng Chia, Wei Yen Lim, Ching-Yu Cheng, Edmund Chan, E Shyong Tai, Tin Aung, Allan Linneberg, Bo Isomaa, Thomas Meitinger, Tiinamaija Tuomi, Liisa Hakaste, Jasmina Kravic, Marit E Jørgensen, Torsten Lauritzen, Panos Deloukas, Kathleen E Stirrups, Katharine R Owen, Andrew J Farmer, Timothy M Frayling, Stephen P O'Rahilly, Mark Walker, Jonathan C Levy, Dylan Hodgkiss, Andrew T Hattersley, Teemu Kuulasmaa, Alena Stančáková, Inês Barroso, Dwaipayan Bharadwaj, Juliana Chan, Giriraj R Chandak, Mark J Daly, Peter J Donnelly, Shah B Ebrahim, Paul Elliott, Tasha Fingerlin, Philippe Froguel, Cheng Hu, Weiping Jia, Ronald C W Ma, Gilean McVean, Taesung Park, Dorairaj Prabhakaran, Manjinder Sandhu, James Scott, Rob Sladek, Nikhil Tandon, Yik Ying Teo, Eleftheria Zeggini, Richard M Watanabe, Heikki A Koistinen, Y Antero Kesaniemi, Matti Uusitupa, Timothy D Spector, Veikko Salomaa, Rainer Rauramaa, Colin N A Palmer, Inga Prokopenko, Andrew D Morris, Richard N Bergman, Francis S Collins, Lars Lind, Erik Ingelsson, Jaakko Tuomilehto, Fredrik Karpe, Leif Groop, Torben Jørgensen, Torben Hansen, Oluf Pedersen, Johanna Kuusisto, Gonçalo Abecasis, Graeme I Bell, John Blangero, Nancy J Cox, Ravindranath Duggirala, Mark Seielstad, James G Wilson, Josee Dupuis, Samuli Ripatti, Craig L Hanis, Jose C Florez, Karen L Mohlke, James B Meigs, Markku Laakso, Andrew P Morris, Michael Boehnke, David Altshuler, Mark I McCarthy, Anna L Gloyn, Cecilia M Lindgren
To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28329397/resveratrol-improves-vascular-function-and-mitochondrial-number-but-not-glucose-metabolism-in-older-adults
#13
Rena M Pollack, Nir Barzilai, Valentin Anghel, Ameya S Kulkarni, Aaron Golden, Pilib O'Broin, David A Sinclair, Michael S Bonkowski, Alexander J Coleville, Danielle Powell, Sharon Kim, Ruin Moaddel, Daniel Stein, Kehao Zhang, Meredith Hawkins, Jill P Crandall
Background: Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive. Methods: In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry...
November 9, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28329165/four-genome-wide-association-studies-identify-new-extreme-longevity-variants
#14
Paola Sebastiani, Anastasia Gurinovich, Harold Bae, Stacy Andersen, Alberto Malovini, Gil Atzmon, Francesco Villa, Aldi T Kraja, Danny Ben-Avraham, Nir Barzilai, Annibale Puca, Thomas T Perls
The search for the genetic determinants of extreme human longevity has been challenged by the phenotype's rarity and its nonspecific definition by investigators. To address these issues, we established a consortium of four studies of extreme longevity that contributed 2,070 individuals who survived to the oldest one percentile of survival for the 1900 U.S. birth year cohort. We conducted various analyses to discover longevity-associated variants (LAV) and characterized those LAVs that differentiate survival to extreme age at death (eSAVs) from those LAVs that become more frequent in centenarians because of mortality selection (eg, survival to younger years)...
October 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27943360/disease-drivers-of-aging
#15
REVIEW
Richard J Hodes, Felipe Sierra, Steven N Austad, Elissa Epel, Gretchen N Neigh, Kristine M Erlandson, Marissa J Schafer, Nathan K LeBrasseur, Christopher Wiley, Judith Campisi, Mary E Sehl, Rosario Scalia, Satoru Eguchi, Balakuntalam S Kasinath, Jeffrey B Halter, Harvey Jay Cohen, Wendy Demark-Wahnefried, Tim A Ahles, Nir Barzilai, Arti Hurria, Peter W Hunt
It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging...
December 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27798627/genome-wide-analysis-identifies-12-loci-influencing-human-reproductive-behavior
#16
Nicola Barban, Rick Jansen, Ronald de Vlaming, Ahmad Vaez, Jornt J Mandemakers, Felix C Tropf, Xia Shen, James F Wilson, Daniel I Chasman, Ilja M Nolte, Vinicius Tragante, Sander W van der Laan, John R B Perry, Augustine Kong, Tarunveer S Ahluwalia, Eva Albrecht, Laura Yerges-Armstrong, Gil Atzmon, Kirsi Auro, Kristin Ayers, Andrew Bakshi, Danny Ben-Avraham, Klaus Berger, Aviv Bergman, Lars Bertram, Lawrence F Bielak, Gyda Bjornsdottir, Marc Jan Bonder, Linda Broer, Minh Bui, Caterina Barbieri, Alana Cavadino, Jorge E Chavarro, Constance Turman, Maria Pina Concas, Heather J Cordell, Gail Davies, Peter Eibich, Nicholas Eriksson, Tõnu Esko, Joel Eriksson, Fahimeh Falahi, Janine F Felix, Mark Alan Fontana, Lude Franke, Ilaria Gandin, Audrey J Gaskins, Christian Gieger, Erica P Gunderson, Xiuqing Guo, Caroline Hayward, Chunyan He, Edith Hofer, Hongyan Huang, Peter K Joshi, Stavroula Kanoni, Robert Karlsson, Stefan Kiechl, Annette Kifley, Alexander Kluttig, Peter Kraft, Vasiliki Lagou, Cecile Lecoeur, Jari Lahti, Ruifang Li-Gao, Penelope A Lind, Tian Liu, Enes Makalic, Crysovalanto Mamasoula, Lindsay Matteson, Hamdi Mbarek, Patrick F McArdle, George McMahon, S Fleur W Meddens, Evelin Mihailov, Mike Miller, Stacey A Missmer, Claire Monnereau, Peter J van der Most, Ronny Myhre, Mike A Nalls, Teresa Nutile, Ioanna Panagiota Kalafati, Eleonora Porcu, Inga Prokopenko, Kumar B Rajan, Janet Rich-Edwards, Cornelius A Rietveld, Antonietta Robino, Lynda M Rose, Rico Rueedi, Kathleen A Ryan, Yasaman Saba, Daniel Schmidt, Jennifer A Smith, Lisette Stolk, Elizabeth Streeten, Anke Tönjes, Gudmar Thorleifsson, Sheila Ulivi, Juho Wedenoja, Juergen Wellmann, Peter Willeit, Jie Yao, Loic Yengo, Jing Hua Zhao, Wei Zhao, Daria V Zhernakova, Najaf Amin, Howard Andrews, Beverley Balkau, Nir Barzilai, Sven Bergmann, Ginevra Biino, Hans Bisgaard, Klaus Bønnelykke, Dorret I Boomsma, Julie E Buring, Harry Campbell, Stefania Cappellani, Marina Ciullo, Simon R Cox, Francesco Cucca, Daniela Toniolo, George Davey-Smith, Ian J Deary, George Dedoussis, Panos Deloukas, Cornelia M van Duijn, Eco J C de Geus, Johan G Eriksson, Denis A Evans, Jessica D Faul, Cinzia Felicita Sala, Philippe Froguel, Paolo Gasparini, Giorgia Girotto, Hans-Jörgen Grabe, Karin Halina Greiser, Patrick J F Groenen, Hugoline G de Haan, Johannes Haerting, Tamara B Harris, Andrew C Heath, Kauko Heikkilä, Albert Hofman, Georg Homuth, Elizabeth G Holliday, John Hopper, Elina Hyppönen, Bo Jacobsson, Vincent W V Jaddoe, Magnus Johannesson, Astanand Jugessur, Mika Kähönen, Eero Kajantie, Sharon L R Kardia, Bernard Keavney, Ivana Kolcic, Päivikki Koponen, Peter Kovacs, Florian Kronenberg, Zoltan Kutalik, Martina La Bianca, Genevieve Lachance, William G Iacono, Sandra Lai, Terho Lehtimäki, David C Liewald, Cecilia M Lindgren, Yongmei Liu, Robert Luben, Michael Lucht, Riitta Luoto, Per Magnus, Patrik K E Magnusson, Nicholas G Martin, Matt McGue, Ruth McQuillan, Sarah E Medland, Christa Meisinger, Dan Mellström, Andres Metspalu, Michela Traglia, Lili Milani, Paul Mitchell, Grant W Montgomery, Dennis Mook-Kanamori, Renée de Mutsert, Ellen A Nohr, Claes Ohlsson, Jørn Olsen, Ken K Ong, Lavinia Paternoster, Alison Pattie, Brenda W J H Penninx, Markus Perola, Patricia A Peyser, Mario Pirastu, Ozren Polasek, Chris Power, Jaakko Kaprio, Leslie J Raffel, Katri Räikkönen, Olli Raitakari, Paul M Ridker, Susan M Ring, Kathryn Roll, Igor Rudan, Daniela Ruggiero, Dan Rujescu, Veikko Salomaa, David Schlessinger, Helena Schmidt, Reinhold Schmidt, Nicole Schupf, Johannes Smit, Rossella Sorice, Tim D Spector, John M Starr, Doris Stöckl, Konstantin Strauch, Michael Stumvoll, Morris A Swertz, Unnur Thorsteinsdottir, A Roy Thurik, Nicholas J Timpson, Joyce Y Tung, André G Uitterlinden, Simona Vaccargiu, Jorma Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Dragana Vuckovic, Johannes Waage, Gert G Wagner, Jie Jin Wang, Nicholas J Wareham, David R Weir, Gonneke Willemsen, Johann Willeit, Alan F Wright, Krina T Zondervan, Kari Stefansson, Robert F Krueger, James J Lee, Daniel J Benjamin, David Cesarini, Philipp D Koellinger, Marcel den Hoed, Harold Snieder, Melinda C Mills
The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort...
December 2016: Nature Genetics
https://www.readbyqxmd.com/read/27744417/lower-circulating-insulin-like-growth-factor-i-is-associated-with-better-cognition-in-females-with-exceptional-longevity-without-compromise-to-muscle-mass-and-function
#17
Leland Perice, Nir Barzilai, Joe Verghese, Erica F Weiss, Roee Holtzer, Pinchas Cohen, Sofiya Milman
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...
October 14, 2016: Aging
https://www.readbyqxmd.com/read/27733457/morbidity-and-mortality-with-cardiac-resynchronization-therapy-with-pacing-vs-with-defibrillation-in-octogenarian-patients-in-a-real-world-setting
#18
Avishag Laish-Farkash, Sharon Bruoha, Amos Katz, Ilan Goldenberg, Mahmoud Suleiman, Yoav Michowitz, Nir Shlomo, Michal Einhorn-Cohen, Vladimir Khalameizer
Aims: Cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D. Methods and results: We compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs...
August 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27535968/strategies-and-challenges-in-clinical-trials-targeting-human-aging
#19
John C Newman, Sofiya Milman, Shahrukh K Hashmi, Steve N Austad, James L Kirkland, Jeffrey B Halter, Nir Barzilai
Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use...
November 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27535967/evaluating-health-span-in-preclinical-models-of-aging-and-disease-guidelines-challenges-and-opportunities-for-geroscience
#20
Derek M Huffman, Jamie N Justice, Michael B Stout, James L Kirkland, Nir Barzilai, Steven N Austad
Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains...
November 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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