publications

2024

1. Ageing as a two-phase process: theoretical framework

   Front. Aging Apr 2024
2. A scenario for an evolutionary selection of ageing

   eLife Apr 2024

2023

1. Alignment-based protein mutational landscape prediction: doing more with less

   Abakarova, Marina, Marquet, Céline, Rera, Michael, Rost, Burkhard, and Laine, Elodie

   Genome Biology and Evolution Nov 2023

   Abs

   The wealth of genomic data has boosted the development of computational methods predicting the phenotypic outcomes of missense variants. The most accurate ones exploit multiple sequence alignments, which can be costly to generate. Recent efforts for democratizing protein structure prediction have overcome this bottleneck by leveraging the fast homology search of MMseqs2. Here, we show the usefulness of this strategy for mutational outcome prediction through a large-scale assessment of 1.5M missense variants across 72 protein families. Our study demonstrates the feasibility of producing alignment-based mutational landscape predictions that are both high-quality and compute-efficient for entire proteomes. We provide the community with the whole human proteome mutational landscape and simplified access to our predictive pipeline.

2. Two phases model of ageing in mice: towards a better identification of age-related and late-life metabolic decline [Registered Report Stage 1 Protocol]

   Cansell, Céline, Goepp, Vivien, Bain, Fanny, Todd, Nicolas, Douard, Veronique, Monnoye, Magali, Sanchez, Clara, Pietrancosta, Nicolas, Rovere, Carole, Denis, Raphael GP, Luquet, Serge, and Rera, Michael

   Aug 2023

   Abs

   Since being described in Drosophila melanogaster in 2011, the Smurf phenotype, has been seen to be evolutionarily conserved in nematode and zebrafish, and has helped to identify the discontinuous nature of ageing and predict impending death from natural causes as well as from environmental stresses. This phenotype allowed us to model ageing as being made of two successive phases : a phase A where individuals are healthy and have no risk of mortality but an age-dependent increasing risk of entering phase B, followed by a phase B where individuals show the so-called hallmarks of ageing and a high risk of death. We will test here whether these two consecutive phases of ageing separated by the Smurf transition are a conserved feature of ageing in the classical mammalian laboratory model Mus musculus. Thanks to a longitudinal longevity study using both males and females from two different mouse genetic backgrounds and by integrating physiological, metabolic and molecular measurements with the life history of approximately 150 mice, we are attempting to identify a phenotypic signature typical of the last phase of life, observable at any chronological age. Validating the two-phase ageing model in a mammalian organism would allow the high risk of imminent death to be better characterized in this model and would extend its implications to a broader range of species for aging research.

3. Drosophilid cuticle pigmentation impacts body temperature

   Freoa, Laurent, Chevin, Luis-Miguel, Christol, Philippe, Méléard, Sylvie, Rera, Michael, Véber, Amandine, and Gibert, Jean-Michel

   Scientific reports Aug 2023

   Abs

   Cuticle pigmentation has been clearly demonstrated to impact body temperature for several relatively large species of insects, but it was questioned for small insects. Here we used a thermal camera to assess the impact of drosophilid cuticle pigmentation on body temperature when individuals are exposed to light. We compared mutants of large effects within species (Drosophila melanogaster ebony and yellow mutants). Then we analyzed the impact of naturally occurring pigmentation variation within species complexes (Drosophila americana/Drosophila novamexicana and Drosophila yakuba/Drosophila santomea). Finally we analyzed lines of D. melanogaster with moderate differences in pigmentation. We found significant differences in temperatures for each of the four pairs we analyzed. The temperature differences appeared to be proportional to the differently pigmented area: between Drosophila melanogaster ebony and yellow mutants or between Drosophila americana and Drosophila novamexicana, for which the whole body is differently pigmented, the difference in temperatures was around 0.6 (p/m 0.2) Celsius degrees. By contrast, between D. yakuba and D. santomea or between Drosophila melanogaster Dark and Pale lines, for which only the posterior abdomen is differentially pigmented, we detected a temperature difference of about 0.14 (p/m 0.10) Celsius degrees. This demonstrates that cuticle pigmentation has ecological implications in drosophilids regarding adaptation to environmental temperature.

4. Smurfness-based two-phase model of ageing helps deconvolve the ageing transcriptional signature

   Zane, Flaminia, Bouzid, Hayet, Sosa Marmol, Sofia, Brazane, Mira, Besse, Savandara, Molina, Julia Lisa, Cansell, Céline, Aprahamian, Fanny, Durand, Sylvère, Ayache, Jessica, Antoniewski, Christophe, Todd, Nicolas, Carré, Clément, and Rera, Michael

   Aging Cell Aug 2023

   Abs

   Abstract Ageing is characterised at the molecular level by six transcriptional ‘hallmarks of ageing’, that are commonly described as progressively affected as time passes. By contrast, the ‘Smurf’ assay separates high-and-constant-mortality risk individuals from healthy, zero-mortality risk individuals, based on increased intestinal permeability. Performing whole body total RNA sequencing, we found that Smurfness distinguishes transcriptional changes associated with chronological age from those associated with biological age. We show that transcriptional heterogeneity increases with chronological age in non-Smurf individuals preceding the other five hallmarks of ageing that are specifically associated with the Smurf state. Using this approach, we also devise targeted pro-longevity genetic interventions delaying entry in the Smurf state. We anticipate that increased attention to the evolutionary conserved Smurf phenotype will bring about significant advances in our understanding of the mechanisms of ageing.

2022

1. Transcriptomic signatures of telomerase-dependent and -independent ageing in the zebrafish gut and brain

   Martins, Raquel Rua, Rera, Michael, and Henriques, Catarina M

   bioRxiv Aug 2022

2021

1. Empowering grassroots innovation to accelerate biomedical research

   Greshake Tzovaras, Bastian, Rera, Michael, Wintermute, Edwin H, Kloppenborg, Katharina, Ferry-Danini, Juliette, Aidelberg, Guy, Aronoff, Rachel, Lindner, Ariel, and Misevic, Dusan

   PLoS Biology Aug 2021

2020

1. Ethical and social implications of approaching death prediction in humans-when the biology of ageing meets existential issues

   Gaille, Marie, Araneda, Marco, Dubost, Clément, Guillermain, Clémence, Kaakai, Sarah, Ricadat, Elise, Todd, Nicolas, and Rera, Michael

   BMC Medical Ethics Aug 2020
2. Conséquences éthiques et sociales de biomarqueurs prédictifs de la mort chez l’homme-La vieillesse et la mort, problématiques comportementales et sociétales

   Gaille, Marie, Araneda, Marco, Dubost, Clément, Guillermain, Clémence, Kaakai, Sarah, Ricadat, Élise, Todd, Nicolas, and Rera, Michael

   médecine/sciences Aug 2020

2019

1. A birth–death model of ageing: from individual-based dynamics to evolutive differential inclusions

   Méléard, Sylvie, Rera, Michael, and Roget, Tristan

   Journal of mathematical biology Aug 2019

2018

1. The Smurf transition: new insights on ageing from end-of-life studies in animal models

   Rera, Michael, Vallot, Céline, and Lefrançois, Christel

   Current opinion in oncology Aug 2018
2. How to catch a smurf?–Ageing and beyond… In vivo assessment of intestinal permeability in multiple model organisms

   Martins, Raquel R, McCracken, Andrew W, Simons, Mirre JP, Henriques, Catarina M, and Rera, Michael

   Bio-protocol Aug 2018
3. Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich’s ataxia

   Palandri, Amandine, Martin, Elodie, Russi, Maria, Rera, Michael, Tricoire, Hervé, and Monnier, Véronique

   Disease models & mechanisms Aug 2018

2017

1. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster

   Rana, Anil, Oliveira, Matheus P, Khamoui, Andy V, Aparicio, Ricardo, Rera, Michael, Rossiter, Harry B, and Walker, David W

   Nature communications Aug 2017

2016

1. Two phases of aging separated by the Smurf transition as a public path to death

   Dambroise, Emilie, Monnier, Lea, Ruisheng, Lu, Aguilaniu, Hugo, Joly, J-S, Tricoire, Herve, and Rera, Michael

   Scientific reports Aug 2016

2015

1. A new, discontinuous 2 phases of aging model: Lessons from Drosophila melanogaster

   Tricoire, Hervé, and Rera, Michael

   PloS one Aug 2015
2. A yeast/Drosophila screen to identify new compounds overcoming frataxin deficiency

   Seguin, Alexandra, Monnier, Véronique, Palandri, Amandine, Bihel, Frédéric, Rera, Michael, Schmitt, Martine, Camadro, Jean-Michel, Tricoire, Hervé, and Lesuisse, Emmanuel

   Oxidative Medicine and Cellular Longevity Aug 2015
3. Distinct shifts in microbiota composition during Drosophila aging impair intestinal function and drive mortality

   Clark, Rebecca I, Salazar, Anna, Yamada, Ryuichi, Fitz-Gibbon, Sorel, Morselli, Marco, Alcaraz, Jeanette, Rana, Anil, Rera, Michael, Pellegrini, Matteo, William, W Ja, and others,

   Cell reports Aug 2015
4. Distinct shifts in microbiota composition during Drosophila aging impair intestinal function and drive mortality. Cell Rep 12: 1656–1667

   Clark, RI, Salazar, A, Yamada, R, Fitz-Gibbon, S, Morselli, M, Alcaraz, J, Rana, A, Rera, M, Pellegrini, M, Ja, WW, and others,

   Aug 2015

2014

1. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner

   Ulgherait, Matthew, Rana, Anil, Rera, Michael, Graniel, Jacqueline, and Walker, David W

   Cell reports Aug 2014

2013

1. Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan

   Rana, Anil, Rera, Michael, and Walker, David W

   Proceedings of the National Academy of Sciences Aug 2013
2. Organ-specific mediation of lifespan extension: more than a gut feeling?

   Rera, Michael, Azizi, Masoud J, and Walker, David W

   Ageing research reviews Aug 2013
3. Increased longevity mediated by yeast NDI1 expression in Drosophila intestinal stem and progenitor cells

   Hur, Jae H, Bahadorani, Sepehr, Graniel, Jacqueline, Koehler, Christopher L, Ulgherait, Matthew, Rera, Michael, Jones, D Leanne, and Walker, David W

   Aging (Albany NY) Aug 2013
4. Why do old flies die?

   Rera, Michael, Clark, Rebecca I, and Walker, David W

   Aging. Aug 2013

2012

1. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila

   Rera, Michael, Clark, Rebecca I, and Walker, David W

   Proceedings of the National Academy of Sciences Aug 2012
2. dJun and Vri/dNFIL3 are major regulators of cardiac aging in Drosophila

   Monnier, Veronique, Iché-Torres, Magali, Rera, Michael, Contremoulins, Vincent, Guichard, Céline, Lalevée, Nathalie, Tricoire, Hervé, and Perrin, Laurent

   PLoS genetics Aug 2012

2011

1. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog

   Rera, Michael, Bahadorani, Sepehr, Cho, Jaehyoung, Koehler, Christopher L, Ulgherait, Matthew, Hur, Jae H, Ansari, William S, Lo Jr, Thomas, Jones, D Leanne, and Walker, David W

   Cell metabolism Aug 2011

2010

1. Mitochondrial electron transport chain dysfunction during development does not extend lifespan in Drosophila melanogaster

   Rera, Michael, Monnier, Véronique, and Tricoire, Hervé

   Mechanisms of ageing and development Aug 2010