ISSN 1662-4009 (online)

ey0016.4-11 | New Mechanisms | ESPEYB16

4.11. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice

K Mao , GF Quipildor , T Tabrizian , A Novaj , F Guan , RO Walters , F Delahaye , GB Hubbard , Y Ikeno , K Ejima , P Li , DB Allison , H Salimi-Moosavi , PJ Beltran , P Cohen , N Barzilai , DM Huffman

To read the full abstract: Nat Commun. 2018 19;9:2394.“Somatopause” causes the physiological decline over time in GH secretion leading to low IGF-I levels in aging subjects. GH has been proposed as an anti-aging therapy, but with no evidence of beneficial effects and with some potential risks [1,2]. Therefore, current guidelines do not recommend GH therapy as anti-aging treatme...

ey0016.5-6 | New Insight into Rare Skeletal Disorders | ESPEYB16

5.6. Gain-of-function mutation of microRNA-140 in human skeletal dysplasia

G Grigelioniene , HI Suzuki , F Taylan , F Mirzamohammadi , ZU Borochowitz , UM Ayturk , S Tzur , E Horemuzova , A Lindstrand , MA Weis , G Grigelionis , A Hammarsjo , E Marsk , A Nordgren , M Nordenskjold , DR Eyre , ML Warman , G Nishimura , PA Sharp , T Kobayashi

Abstract: Nat Med. 2019 Apr;25(4):583–590. PMID: 30804514In brief: This study describes the first skeletal dysplasia caused by a mutation in a microRNA that is not simply inactivating, but modifies the repertoire of target genes.Comment: MicroRNAs (miRNAs) are small (20–24 nucleotides) noncoding RNA molecules that post-transcriptio...

ey0016.5-16 | Basic Science - Bone | ESPEYB16

5.16. Discovery of a periosteal stem cell mediating intramembranous bone formation

S Debnath , AR Yallowitz , J McCormick , S Lalani , T Zhang , R Xu , N Li , Y Liu , YS Yang , M Eiseman , JH Shim , M Hameed , JH Healey , MP Bostrom , DA Landau , MB Greenblatt

Abstract: Nature. 2018 Oct;562(7725):133–139.In brief: A newly discovered periosteal stem cell pool with features distinct from other skeletal mesenchymal stem cells (MSCs) is present in murine and human bone and reveals a pivotal function in intramembranous ossification, cortical bone architecture and fracture healing in conditional knockout mouse strains.</st...

ey0016.5-18 | Basic Science - Bone | ESPEYB16

5.18. Developmental origin, functional maintenance and genetic rescue of osteoclasts

CE Jacome-Galarza , GI Percin , JT Muller , E Mass , T Lazarov , J Eitler , M Rauner , VK Yadav , L Crozet , M Bohm , PL Loyher , G Karsenty , C Waskow , F Geissmann

Abstract: Nature. 2019 Apr;568(7753):541–545.In brief: Murine knockout studies unravel the developmental origin of osteoclasts in embryonic, erythro-myeloid progenitors, acquiring exceptional longevity by constant fusion with monocytes and rejuvenation of cellular nucleii throughout postnatal life.Comment: Osteoclast function is essentia...

ey0016.6-3 | New Functions of (Old) Genes | ESPEYB16

6.3. Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9

B Croft , T Ohnesorg , J Hewitt , J Bowles , A Quinn , J Tan , V Corbin , E Pelosi , J van den Bergen , R Sreenivasan , I Knarston , G Robevska , DC Vu , J Hutson , V Harley , K Ayers , P Koopman , A Sinclair

Nat Commun. 2018 Dec 14;9(1):5319.doi: 10.1038/s41467-018-07784-9. PubMed [citation] PMID: 30552336Initial steps in the sex determination of the (human) testis depend on SRY regulating SOX9, but the exact mechanism that controls SOX9 expression remains unknown. These authors discovered four overlapping copy number variations (CNVs) upstr...

ey0016.8-16 | New Paradigms | ESPEYB16

8.16. Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans

H Vaeroy , C Adori , R Legrand , N Lucas , J Breton , C Cottard , Rego JC do , C Duparc , E Louiset , H Lefebvre , P Dechelotte , E Western , S Andersson , T Hokfelt , SO Fetissov

To read the full abstract: Proc Natl Acad Sci U S A. 2018; 115(28): E6576–E6584.It is accepted that aggressive behavior can be viewed as a strategy by humans and animals to cope with stress, implying that neurobiological mechanisms involved in stress responses should underlie both physiological and pathological aggression (15, 16). The hypothalamic–pituitary–adrenal ...

ey0016.12-5 | Type 2 Diabetes | ESPEYB16

12.5. Liraglutide in children and adolescents with type 2 diabetes

WV Tamborlane , M Barrientos-Perez , U Fainberg , H Frimer-Larsen , M Hafez , PM Hale , MY Jalaludin , M Kovarenko , I Libman , JL Lynch , P Rao , N Shehadeh , S Turan , D Weghuber , T Barrett , I Ellipse Trial

N Engl J Med 2019; 10.1056/NEJMoa1903822.DOI: 10.1056/NEJMoa1903822http://www.ncbi.nlm.nih.gov/pubmed/31034184Summary: In a double-blind, randomized, phase 3 trial, 135 overweight and obese adolescents, aged 10 to 17 years with T2DM, were randomly assigned to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo, bot...

ey0016.12-7 | Metabolic Syndrome | ESPEYB16

12.7. Prospective associations between socioeconomically disadvantaged groups and metabolic syndrome risk in European children. Results from the IDEFICS study

I Iguacel , N Michels , W Ahrens , K Bammann , G Eiben , JM Fernandez-Alvira , S Marild , D Molnar , L Reisch , P Russo , M Tornaritis , T Veidebaum , M Wolters , LA Moreno , C Bornhorst , IDEFICS consortium Bornhorst

To read the full abstract: Int J Cardiol 2018;272:333–340.Summary: In a multi-center prospective cohort study of 2401 European children, early life exposure to socioeconomic disadvantages, particularly living in low-educated families, having a non-traditional family structure, parental unemployment and the accumulation of >3 disadvantages were associated with higher ris...

ey0016.12-13 | Lipid Metabolism | ESPEYB16

12.13. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer

JE Manson , NR Cook , IM Lee , W Christen , SS Bassuk , S Mora , H Gibson , CM Albert , D Gordon , T Copeland , D D'Agostino , G Friedenberg , C Ridge , V Bubes , EL Giovannucci , WC Willett , JE Buring , VITAL Research Group Buring

To read the full abstract: N Engl J Med 2019;380:23-32.Summary: In this randomized primary prevention placebo-controlled trial of 25,871 US adults, with a two-by-two factorial design, supplements with omega-3 did not lower the overall incidence of adverse cardiovascular events or cancer compared to a placebo.Comment: Omega-3 fatty acids are polyun...

ey0016.15-2 | (1) | ESPEYB16

15.2. Vitamin D supplements and prevention of cancer and cardiovascular disease

JE Manson , NR Cook , IM Lee , W Christen , SS Bassuk , S Mora , H Gibson , D Gordon , T Copeland , D D'Agostino , G Friedenberg , C Ridge , V Bubes , EL Giovannucci , WC Willett , JE Buring

To read the full abstract: N Engl J Med 2019;380:33–44This paper describes a large randomized, placebo-controlled trial of vitamin D3 (cholecalciferol) 2000 IU per day in 25,871 US adults. After median follow-up of 5.3 years, supplementation with vitamin D did not alter the risk of the primary end points, invasive cancer of any type hazard ratio, 0.96; 95% confidence interval [CI], ...