| EMBO Press

This collection of EMBO press articles invites you to explore exciting recent findings related to the biology of aging and cellular senescence. The topics covered range from control of genome stability and chromatin to metabolic plasticity during healthy aging, characterisation of long-lived model animals and molecular lessons from pathological conditions such as tau aggregation and telomere dysfunction during lifespan. The collection also interrogates new therapy angles in immunoaging and longitudinal consequences of anti-cancer treatments. We hope that you enjoy reading the articles and we welcome your own contributions. Image © SciStories LLC.

Featured Articles

A variant of SIRT6 is enriched in human centenarians that show enhanced mono‐ADP ribosylase activity, but a reduced deacetylase activity; leading to the generation of an allele that promotes enhanced DNA repair, suppression of transposable elements, and resistance to oxidative stress.
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
A variant of SIRT6 is enriched in human centenarians that show enhanced mono‐ADP ribosylase activity, but a reduced deacetylase activity; leading to the generation of an allele that promotes enhanced DNA repair, suppression of transposable elements, and resistance to oxidative stress.
The matricellular protein fibulin 7 is required for the long‐term maintenance of epidermal stem cell heterogeneity and skin regenerative capacity by supporting ECM organization.
The extracellular matrix fibulin 7 maintains epidermal stem cell heterogeneity during skin aging
The matricellular protein fibulin 7 is required for the long‐term maintenance of epidermal stem cell heterogeneity and skin regenerative capacity by supporting ECM organization.
Irradiation‐induced alopecia and dermatitis (IRIAD) represent two of the most prominent side effects of radiotherapy in the skin. In this study, Paldor et al applied scRNA‐seq analysis to identify driving factors of IRIAD in order to facilitate the development of targeted therapeutic approaches for its prevention.
Single‐cell transcriptomics reveals a senescence‐associated IL‐6/CCR6 axis driving radiodermatitis
Irradiation‐induced alopecia and dermatitis (IRIAD) represent two of the most prominent side effects of radiotherapy in the skin. In this study, Paldor et al applied scRNA‐seq analysis to identify driving factors of IRIAD in order to facilitate the development of targeted therapeutic approaches for its prevention.
Profiling the chromatin landscape and nascent transcriptome in murine liver reveals an age‐related increase in chromatin accessibility at promoters and enhancers and a decrease in promoter‐proximal pausing of RNA polymerase II due to decreased pausing complex stability.
Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver
Profiling the chromatin landscape and nascent transcriptome in murine liver reveals an age‐related increase in chromatin accessibility at promoters and enhancers and a decrease in promoter‐proximal pausing of RNA polymerase II due to decreased pausing complex stability.
Exposure of mesenchymal stem cells to normoxia impairs osteogenic differentiation due to altered acetyl‐CoA localization within the cell.
Hypoxia promotes osteogenesis by facilitating acetyl‐CoA‐mediated mitochondrial–nuclear communication
Exposure of mesenchymal stem cells to normoxia impairs osteogenic differentiation due to altered acetyl‐CoA localization within the cell.
This study reveals a link between early‐life treatments and long‐term effects on lifespan in Drosophila and mice.
Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster
This study reveals a link between early‐life treatments and long‐term effects on lifespan in Drosophila and mice.
This review summarizes the clinical translation of gene therapy and cochlear implant innovations and discusses if there is an unmet medical need for improving hearing restoration.
Is there an unmet medical need for improved hearing restoration?
This review summarizes the clinical translation of gene therapy and cochlear implant innovations and discusses if there is an unmet medical need for improving hearing restoration.
Integrating different genome‐wide data can be powerful in assessing age‐related tissue dysfunction. In their recent study, Tessarz and colleagues (Bozukova et al, 2022) report increased chromatin accessibility in aged mouse liver, which is however not accompanied by increased transcriptional output.
Keep calm and transcribe on: chromatin changes with age, but transcription can learn to live with it
- Cian J Lynch
- Manuel Serrano
Integrating different genome‐wide data can be powerful in assessing age‐related tissue dysfunction. In their recent study, Tessarz and colleagues (Bozukova et al, 2022) report increased chromatin accessibility in aged mouse liver, which is however not accompanied by increased transcriptional output.
The unfolded protein response signaling components IRE1 and XBP1 are shown to play a role in age‐associated cognitive function and brain health in mice.
Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging
The unfolded protein response signaling components IRE1 and XBP1 are shown to play a role in age‐associated cognitive function and brain health in mice.
Methylglyoxal accumulation promotes a pro‐inflammatory microenvironment in pancreatic islets of mice, leading to an age‐dependent impairment of glucose‐stimulated insulin secretion (GSIS) and glucose tolerance in mice.
Glyoxalase 1 knockdown induces age‐related β‐cell dysfunction and glucose intolerance in mice
Methylglyoxal accumulation promotes a pro‐inflammatory microenvironment in pancreatic islets of mice, leading to an age‐dependent impairment of glucose‐stimulated insulin secretion (GSIS) and glucose tolerance in mice.
In this Commentary, M. Mittelbrunn, E Gabandé‐Rodríguez and M. Pffeifer discuss T cell‐based immunotherapy for age‐related diseases.
Immuno(T)herapy for age‐related diseases
In this Commentary, M. Mittelbrunn, E Gabandé‐Rodríguez and M. Pffeifer discuss T cell‐based immunotherapy for age‐related diseases.
Mammalian cell senescence entry is marked by the nuclear loss of HMGB1. Genome‐wide analyses show that HMGB1 binds both chromatin and mRNAs in proliferating cells, and its loss underlies topological and splicing changes inducing the senescent transcriptional program.
HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence
Mammalian cell senescence entry is marked by the nuclear loss of HMGB1. Genome‐wide analyses show that HMGB1 binds both chromatin and mRNAs in proliferating cells, and its loss underlies topological and splicing changes inducing the senescent transcriptional program.

Tau diffuses and organizes in nanometer‐sized clusters near the plasma membrane that show distinct kinetic behaviors.
Single‐molecule imaging reveals Tau trapping at nanometer‐sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion
Tau diffuses and organizes in nanometer‐sized clusters near the plasma membrane that show distinct kinetic behaviors.
In‐depth profiling of the naked mole‐rat hematopoietic system by surface marker analysis and single‐cell sequencing uncovers resilience phenotypes and unexpected similarities with humans.
Characterization of naked mole‐rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits
In‐depth profiling of the naked mole‐rat hematopoietic system by surface marker analysis and single‐cell sequencing uncovers resilience phenotypes and unexpected similarities with humans.
Recent single‐cell profiling uncovers distinct features and ageing dynamics of the exceptionally long‐lived rodent's haematopoiesis.
Living a longer life: unique lessons from the naked mole‐rat blood system
- Rebecca Andersson
- Maria Carolina Florian
Recent single‐cell profiling uncovers distinct features and ageing dynamics of the exceptionally long‐lived rodent's haematopoiesis.
Immunohistochemical analysis combined with genetic fate‐mapping, behaviour, imaging, and single cell transcriptomics show that astrogenesis persists to old age and is responsive to environmental and behavioural stimuli.
Astrogenesis in the murine dentate gyrus is a life‐long and dynamic process
Immunohistochemical analysis combined with genetic fate‐mapping, behaviour, imaging, and single cell transcriptomics show that astrogenesis persists to old age and is responsive to environmental and behavioural stimuli.
Expression profiling of worm ageing uncovers common and organ‐specific molecular pathways involved in health deterioration.
Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans
Expression profiling of worm ageing uncovers common and organ‐specific molecular pathways involved in health deterioration.
Extrachromosomal DNA circles, a hallmark of alternative telomere lengthening (ALT), arise also in telomerase‐deficient yeast cells and may aid recombination‐based telomere maintenance.
Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae
Extrachromosomal DNA circles, a hallmark of alternative telomere lengthening (ALT), arise also in telomerase‐deficient yeast cells and may aid recombination‐based telomere maintenance.
While senescence‐linked inflammatory phenotypes caused by classical cancer drugs can be pro‐tumorigenic, senescence induced by CDK4/6 inhibitors lacks NF‐kB‐associated secretory phenotypes and is well tolerated in vivo.
Pharmacological CDK4/6 inhibition reveals a p53‐dependent senescent state with restricted toxicity
While senescence‐linked inflammatory phenotypes caused by classical cancer drugs can be pro‐tumorigenic, senescence induced by CDK4/6 inhibitors lacks NF‐kB‐associated secretory phenotypes and is well tolerated in vivo.

EMBO Reports

Progressive increase of HDAC activity in Fibro‐adipogenic progenitors from Duchenne Muscular Dystrophy model mice leads to altered histone acetylation profiles associated with senescence at late disease stages that are not fully reversed by HDAC inhibitors.
Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro‐adipogenic progenitors
Progressive increase of HDAC activity in Fibro‐adipogenic progenitors from Duchenne Muscular Dystrophy model mice leads to altered histone acetylation profiles associated with senescence at late disease stages that are not fully reversed by HDAC inhibitors.
Mitochondrial function influences survival and stress resilience in Caenorhabditis elegans. cest‐2.2 overexpression promotes mobilization of lipid deposits and extends lifespan of complex I deficient mutants.
CEST‐2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants
Mitochondrial function influences survival and stress resilience in Caenorhabditis elegans. cest‐2.2 overexpression promotes mobilization of lipid deposits and extends lifespan of complex I deficient mutants.
Mitochondrial alterations and increased inflammation in Npm1 cKO mice result in HSC aging and MDS‐like phenotypes. p53 dependent responses in Npm1 cKO mice lead to bone marrow failure, while Npm1/p53 double KO mice develop leukemia.
NPM1 ablation induces HSC aging and inflammation to develop myelodysplastic syndrome exacerbated by p53 loss
Mitochondrial alterations and increased inflammation in Npm1 cKO mice result in HSC aging and MDS‐like phenotypes. p53 dependent responses in Npm1 cKO mice lead to bone marrow failure, while Npm1/p53 double KO mice develop leukemia.
Deficiency in a key familial Parkinson’s disease gene, PARK7/DJ‐1, reduces immunoaging in T cell compartments of both human and mice at both cellular phenotypic and functional levels.
DJ‐1 depletion prevents immunoaging in T‐cell compartments
Deficiency in a key familial Parkinson’s disease gene, PARK7/DJ‐1, reduces immunoaging in T cell compartments of both human and mice at both cellular phenotypic and functional levels.
During aging, telomere dysfunction accumulates and activates a DNA damage response, leading to increase of ACE2, the human SARS‐CoV‐2 receptor. This mechanism may explain the higher susceptibility of elderly to COVID‐19.
DNA damage response at telomeres boosts the transcription of SARS‐CoV‐2 receptor ACE2 during aging
During aging, telomere dysfunction accumulates and activates a DNA damage response, leading to increase of ACE2, the human SARS‐CoV‐2 receptor. This mechanism may explain the higher susceptibility of elderly to COVID‐19.
Deficient DNA damage repair underlies neurological disorders and age‐associated neurodegenerative diseases. This review discusses our current understanding of how the genomic location of DNA damage and defunctional repair proteins impact neuron health.
Mechanisms of DNA damage‐mediated neurotoxicity in neurodegenerative disease
- Gwyneth Welch
- Li‐Huei Tsai
Deficient DNA damage repair underlies neurological disorders and age‐associated neurodegenerative diseases. This review discusses our current understanding of how the genomic location of DNA damage and defunctional repair proteins impact neuron health.

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Leveraging prior knowledge to infer gene regulatory networks from single-cell RNA-sequencing data

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Articles13 February 2025
Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation

Autophagy & Cell Death Biomarkers Biotechnology & Synthetic Biology Cancer Cardiovascular System Cell Adhesion, Polarity & Cytoskeleton Cell Cycle Chromatin, Transcription & Genomics Computational Biology Development Digestive System DNA Replication, Recombination & Repair Evolution & Ecology Genetics, Gene Therapy & Genetic Disease Haematology Immunology Membranes & Trafficking Metabolism Methods & Resources Microbiology, Virology & Host Pathogen Interaction Molecular Biology of Disease Musculoskeletal System Neuroscience Organelles Pharmacology & Drug Discovery Plant Biology Post-translational Modifications & Proteolysis Proteomics Respiratory System RNA Biology Signal Transduction Skin Stem Cells & Regenerative Medicine Structural Biology Translation & Protein Quality Urogenital System Vascular Biology & Angiogenesis

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Aging & Senescence (2022)

Featured Articles

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A

The extracellular matrix fibulin 7 maintains epidermal stem cell heterogeneity during skin aging

Single‐cell transcriptomics reveals a senescence‐associated IL‐6/CCR6 axis driving radiodermatitis

Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver

Hypoxia promotes osteogenesis by facilitating acetyl‐CoA‐mediated mitochondrial–nuclear communication

Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster

Is there an unmet medical need for improved hearing restoration?

Keep calm and transcribe on: chromatin changes with age, but transcription can learn to live with it

Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging

Glyoxalase 1 knockdown induces age‐related β‐cell dysfunction and glucose intolerance in mice

Immuno(T)herapy for age‐related diseases

HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence

Further Reading

The EMBO Journal

Single‐molecule imaging reveals Tau trapping at nanometer‐sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion

Characterization of naked mole‐rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits

Living a longer life: unique lessons from the naked mole‐rat blood system

Astrogenesis in the murine dentate gyrus is a life‐long and dynamic process

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans

Telomeric C‐circles localize at nuclear pore complexes in Saccharomyces cerevisiae

Pharmacological CDK4/6 inhibition reveals a p53‐dependent senescent state with restricted toxicity

EMBO Reports

Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro‐adipogenic progenitors

CEST‐2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants

NPM1 ablation induces HSC aging and inflammation to develop myelodysplastic syndrome exacerbated by p53 loss

DJ‐1 depletion prevents immunoaging in T‐cell compartments

DNA damage response at telomeres boosts the transcription of SARS‐CoV‐2 receptor ACE2 during aging

Mechanisms of DNA damage‐mediated neurotoxicity in neurodegenerative disease

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Modulation of tumor inflammatory signaling and drug sensitivity by CMTM4

LATS1/2 inactivation in the mammary epithelium drives the evolution of a tumor-associated niche

Leveraging prior knowledge to infer gene regulatory networks from single-cell RNA-sequencing data

Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation

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EDITOR CONFERENCE CALENDAR

EMBO Workshop: Neural development and neurodegeneration

International Titisee Conference: Stress signaling in development & disease

SY-Stem 2025

Keystone Symposium: Myeloid Cells

Keystone Symposium: Precision Genome Engineering

Keystone Symposium: Obesity and Adipose Tissue

Keystone Symposium - B Cells: Multifaceted Functions and Dysfunctions

Keystone Symposium - Human Microbiome: Diversity, Selection and Adaptation

Keystone Symposium - Tuberculosis: Heterogeneity from Experimental Models to Human Disease

EMBO Workshop: Energy balance in metabolic diseases

GRC: Mammalian DNA Repair Conference

GRCL 6th international cancer symposium

EACR-AstraZeneca Conference: Circulating Nucleic Acids (cfDNA/ctDNA)

Keystone Symposia: Non-coding RNA Biology

Cell Bio 2024 - An ASCB | EMBO Meeting

VIB: Next-Generation Synthetic Biology

53rd Annual Meeting of the Japanese Society for Immunology

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