Physiology

Impaired iron recycling from erythrocytes is an early hallmark of aging

1. Patryk Slusarczyk
2. Pratik Kumar Mandal
3. Gabriela Zurawska
4. Marta Niklewicz
5. Komal Chouhan
6. Raghunandan Mahadeva
7. Aneta Jończy
8. Matylda Macias
9. Aleksandra Szybinska
10. Magdalena Cybulska-Lubak
11. Olga Krawczyk
12. Sylwia Herman
13. Michal Mikula
14. Remigiusz Serwa
15. Małgorzata Lenartowicz
16. Wojciech Pokrzywa
17. Katarzyna Mleczko-Sanecka

• Curated by eLife

  eLife assessment

  Slusarczyk et al demonstrate that red pulp macrophages (RPM), specialized splenic cells that clear senescent red blood cells through erythrophagocytosis, show diminished function in aging mice. This impairment leads to retention of hemolytic red blood cells and formation of extracellular aggregates which further exacerbate RPM demise. Iron restriction alleviates most of these symptoms in aging RPMs. They propose RPM collapse as an early indicator of aging that could be reversed through iron limitation.

Reviewed by eLife

Vitamin B2 enables regulation of fasting glucose availability

1. Peter M Masschelin
2. Pradip Saha
3. Scott A Ochsner
4. Aaron R Cox
5. Kang Ho Kim
6. Jessica B Felix
7. Robert Sharp
8. Xin Li
9. Lin Tan
10. Jun Hyoung Park
11. Liping Wang
12. Vasanta Putluri
13. Philip L Lorenzi
14. Alli M Nuotio-Antar
15. Zheng Sun
16. Benny Abraham Kaipparettu
17. Nagireddy Putluri
18. David D Moore
19. Scott A Summers
20. Neil J McKenna
21. Sean M Hartig

• Curated by eLife

  eLife assessment

  Masschelin et al. investigate the role of Vitamin B2 (riboflavin), an essential cofactor for FAD and FMN coenzymes involved in the electron transport chain and TCA cycle, in fasting glucose metabolism. This study phenotypes B2-deficient mice liver and provides valuable data on genes and metabolites that are changed with B2 depletion +/- Fenofibrate administration. The work employs solid methodology and will be of interest to liver physiologists interested in fasting in the context of PPAR.

Reviewed by eLife

An automated feeding system for the African killifish reveals the impact of diet on lifespan and allows scalable assessment of associative learning

1. Andrew McKay
2. Emma K Costa
3. Jingxun Chen
4. Chi-Kuo Hu
5. Xiaoshan Chen
6. Claire N Bedbrook
7. Rishad C Khondker
8. Mike Thielvoldt
9. Param Priya Singh
10. Tony Wyss-Coray
11. Anne Brunet

• Curated by eLife

  eLife assessment

  McKay, et al. describe development of a new wireless, network-enabled automated feeder system with which diet amount and schedule can be controlled across individually housed killifish. The system is constructed using open-source components and software and is amenable to manufacture by individual research groups and is highly scalable. The authors then use this system to explore dietary restriction effects on killifish lifespan and to develop an associative learning assay, two important goals in the KF /longevity field. The authors demonstrate that precise control of food allows automated investigation of lifespan extension under calorie restriction conditions. Secondly, they show an exciting modification of the system that involves only addition of a simple LED light. This modification allows use of the system in an associative learning / conditioning paradigm. Finally, using this paradigm, they demonstrate an age-dependent decline in learning.

Reviewed by eLife

Age-associated sleep-wake patterns are altered with Prdm13 signaling in the dorsomedial hypothalamus and dietary restriction in mice

1. Shogo Tsuji
2. Cynthia S Brace
3. Ruiqing Yao
4. Yoshitaka Tanie
5. Hirobumi Tada
6. Nicholas Rensing
7. Seiya Mizuno
8. Julio Almunia
9. Yingyi Kong
10. Kazuhiro Nakamura
11. Noboru Ogiso
12. Shinya Toyokuni
13. Satoru Takahashi
14. Michael Wong
15. Shin-ichiro Imai
16. Akiko Satoh

Reviewed by Review Commons, PREreview

Tenotomy-induced muscle atrophy is sex-specific and independent of NFκB

1. Gretchen A Meyer
2. Stavros Thomopoulos
3. Yousef Abu-Amer
4. Karen C Shen

• Curated by eLife

  eLife assessment

  The purpose of the study was to evaluate the transcription factor NF-kB, a common transcription factor that is thought to mediate muscle atrophy, in the setting of a rotator cuff injury. The authors used gain of function and loss of function NF-kB inhibitors to show that, surprisingly, NF-kB does not seem to be a major mediator of muscle atrophy in this model (as compared to other atrophy models), but there are sex-related differences. They found that male mice were more likely to have atrophy regulated by autophagy, both of which are interesting, novel findings.

Reviewed by eLife

A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice

1. Reem Abdel-Haq
2. Johannes CM Schlachetzki
3. Joseph C Boktor
4. Thaisa M Cantu-Jungles
5. Taren Thron
6. Mengying Zhang
7. John W Bostick
8. Tahmineh Khazaei
9. Sujatha Chilakala
10. Livia H Morais
11. Greg Humphrey
12. Ali Keshavarzian
13. Jonathan E Katz
14. Matthew Thomson
15. Rob Knight
16. Viviana Gradinaru
17. Bruce R Hamaker
18. Christopher K Glass
19. Sarkis K Mazmanian

• Curated by eLife

  eLife assessment

  The complex mechanisms through which diet impact Parkinson's Disease are unclear, limiting the ability to guide patients to an optimal diet. Here, researchers use a mouse model to test the impact of dietary fiber, revealing changes in gut microbes and immune cells in the brain. This study raises intriguing hypotheses about how diet-induced changes in the microbiome could lead to changes in brain function.

Reviewed by eLife

Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel

1. Peter R Strege
2. Luke M Cowan
3. Constanza Alcaino
4. Amelia Mazzone
5. Christopher A Ahern
6. Lorin S Milescu
7. Gianrico Farrugia
8. Arthur Beyder

• Curated by eLife

  eLife Assessment:

  This manuscript presents a biophysical study of the nature of the mechanosensitivity of voltage-gated sodium channels. The identification of a voltage-independent mechanosensitive step is well founded, the proposal that this step is the intracellular gate is plausible speculation. It is expected to be of interest to scientists studying the physical basis of mechanosensitivity in electrophysiology.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation

1. Phoebe M Kirkwood
2. Douglas A Gibson
3. Isaac Shaw
4. Ross Dobie
5. Olympia Kelepouri
6. Neil C Henderson
7. Philippa TK Saunders

• Curated by eLife

  Evaluation Summary:

  This is an important and delicately designed study that uses integrated tools to reveal underlying mechanisms of repair of the endometrium at menstruation. It combines single cell sequencing analysis and lineage tracing technologies to strongly prove that repair-specific cells originate from the fibroblast cell clusters and PDGFRα+ endometrial fibroblasts undergo MET and can become incorporated into the luminal epithelium of the post repair tissue.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Hepatic inactivation of murine Surf4 results in marked reduction in plasma cholesterol

1. Vi T Tang
2. Joseph McCormick
3. Bolin Xu
4. Yawei Wang
5. Huan Fang
6. Xiao Wang
7. David Siemieniak
8. Rami Khoriaty
9. Brian T Emmer
10. Xiao-Wei Chen
11. David Ginsburg

• Curated by eLife

  Evaluation Summary:

  By the use of liver specific gene knock-out approaches Tang et al have clearly documented an important role for an endoplasmic reticulum sorting receptor, SURF4, in the efficient secretion of PCSK9, a protein in circulation that binds to and enhances the intracellular uptake and degradation of the low density lipoprotein receptor. As a consequence of liver specific knock-outs, adult mice survive well with an exceptionally lower level of circulating cholesterol, triglycerides and various lipoproteins. These compelling results reinforce the prospect for the development of therapeutic approaches in cholesterol and LDL reduction by targeting the intracellular association of PCSK9 and the SURF4 receptor. The work is elegant and complete with the only concern that some of the work and results overlap work published previously by some of these authors.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

1. Karla J Suchacki
2. Benjamin J Thomas
3. Yoshiko M Ikushima
4. Kuan-Chan Chen
5. Claire Fyfe
6. Adriana AS Tavares
7. Richard J Sulston
8. Andrea Lovdel
9. Holly J Woodward
10. Xuan Han
11. Domenico Mattiucci
12. Eleanor J Brain
13. Carlos J Alcaide-Corral
14. Hiroshi Kobayashi
15. Gillian A Gray
16. Phillip D Whitfield
17. Roland H Stimson
18. Nicholas M Morton
19. Alexandra M Johnstone
20. William P Cawthorn

Reviewed by Review Commons