Series 13 September 2021

Molecular ageing

As the burden of ageing-associated disorders is increasing, so is our understanding of the molecular and cellular changes that occur during ageing. This knowledge has important medical and social implications as it has the potential of being exploited to delay ageing and the onset of ageing-associated disorders. Nature Reviews Molecular Cell Biology presents a series of Reviews and Comments on the current understanding of ageing at the molecular level, and on how targeting these ageing-associated changes might increase healthspan and lifespan.

Reviews & Comments

FOXO transcription factors as mediators of stress adaptation

Forkhead box (FOXO) transcription factors are important mediators of cell stress responses, generally considered to preserve homeostasis and counteract ageing. However, FOXO-mediated mechanisms can also support the survival of cancer and other dysfunctional cells, thereby complicating the link between FOXOs and lifespan extension.
- Maria J. Rodriguez-Colman
- Tobias B. Dansen
- Boudewijn. M. T. Burgering
Review Article14 Sep 2023 Nature Reviews Molecular Cell Biology
Ageing and rejuvenation of tissue stem cells and their niches

Stem cell function declines during ageing, resulting in the loss of tissue integrity and health deterioration. Ageing is associated with defects in the maintenance of stem cell quiescence and cell differentiation ability, clonal expansion and infiltration of immune cells in the niche. This Review discusses the mechanisms underlying ageing in stem cells and their niches, and potential rejuvenation strategies.
- Anne Brunet
- Margaret A. Goodell
- Thomas A. Rando
Review Article20 Jul 2022 Nature Reviews Molecular Cell Biology
Molecular mechanisms of dietary restriction promoting health and longevity

Dietary restriction in rodents and non-human primates affects key nutrient-sensing signalling pathways to increase healthspan and lifespan. This Review discusses these geroprotective mechanisms and recent insights suggesting that dietary restriction results in similar molecular and metabolic changes in humans, contributing to the prevention of ageing-associated diseases.
- Cara L. Green
- Dudley W. Lamming
- Luigi Fontana
Review Article13 Sep 2021 Nature Reviews Molecular Cell Biology
NAD⁺ metabolism and its roles in cellular processes during ageing

Nicotinamide adenine dinucleotide (NAD⁺) is a central redox factor and enzymatic cofactor that functions in a plethora of cellular processes, including metabolic pathways and DNA metabolism, and affects cell fate and function. NAD⁺ levels gradually decline with age, and therapeutic elevation of NAD⁺ levels is being trialled for extending human healthspan and lifespan.
- Anthony J. Covarrubias
- Rosalba Perrone
- Eric Verdin
Review Article22 Dec 2020 Nature Reviews Molecular Cell Biology
Cellular senescence in ageing: from mechanisms to therapeutic opportunities

Cellular senescence is characterized by a permanent proliferation arrest and the establishment of a senescence-associated secretory phenotype. This Review discusses the mechanisms of cellular senescence and induction of a senescence-associated secretory phenotype, recent insights into how senescence contributes to ageing, and the potential of senolytic and senomorphic therapies in ageing and associated diseases.
- Raffaella Di Micco
- Valery Krizhanovsky
- Fabrizio d’Adda di Fagagna
Review Article16 Dec 2020 Nature Reviews Molecular Cell Biology
Old and new models for the study of human ageing

Anne Brunet discusses the different model organisms that are used for the study of ageing mechanisms and their advantages and disadvantages.
- Anne Brunet
Comment22 Jun 2020 Nature Reviews Molecular Cell Biology
The ageing epigenome and its rejuvenation

Ageing is characterized by the functional decline of tissues and organs and increased risk of ageing-associated disorders, and this decline is associated with epigenetic changes. Recently, ‘rejuvenating’ interventions, such as metabolic manipulation, partial cell reprogramming, heterochronic parabiosis and senescent cell ablation, have been proposed to extend healthspan and lifespan by modulating the epigenome.
- Weiqi Zhang
- Jing Qu
- Juan Carlos Izpisua Belmonte
Review Article4 Feb 2020 Nature Reviews Molecular Cell Biology
mTOR at the nexus of nutrition, growth, ageing and disease

The mTOR pathway integrates diverse environmental cues to control biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing, and is thus a promising target for pharmacological intervention.
- Grace Y. Liu
- David M. Sabatini
Review Article14 Jan 2020 Nature Reviews Molecular Cell Biology
The roles of DNA, RNA and histone methylation in ageing and cancer

The dynamic methylation of chromatin components — DNA, histones and RNA — is crucial in development, ageing and cancer. Therapies that target regulators of DNA and histone methylation in cancer have recently been developed. These promising therapies, which include strategies that may improve tumour immune surveillance, are already being tested in early-phase clinical trials.
- Ewa M. Michalak
- Marian L. Burr
- Mark A. Dawson
Review Article3 Jul 2019 Nature Reviews Molecular Cell Biology
Decelerating ageing and biological clocks by autophagy

Kroemer and Lopez-Otín discuss how the induction of autophagy could slow down human ageing and thus also delay the onset of ageing-associated diseases, by decelerating biological clocks.
- Carlos Lopez-Otín
- Guido Kroemer
Comment4 Jun 2019 Nature Reviews Molecular Cell Biology
Cellular senescence causes ageing

Jesús Gil discusses the first evidence for cellular senescence being associated with ageing, and how these studies opened new routes for basic and translational research.
- Jesús Gil
Journal Club8 Apr 2019 Nature Reviews Molecular Cell Biology
The proteostasis network and its decline in ageing

Misfolded proteins have a high propensity to form potentially toxic aggregates. Cells employ a complex network of processes, involving chaperones and proteolytic machineries that ensure proper protein folding and remodel or degrade misfolded species and aggregates. This proteostasis network declines with age, which can be linked to human degenerative diseases.
- Mark S. Hipp
- Prasad Kasturi
- F. Ulrich Hartl
Review Article7 Feb 2019 Nature Reviews Molecular Cell Biology
Haematopoietic stem cell activity and interactions with the niche

The haematopoietic stem cell (HSC) niche in the bone marrow ensures haematopoiesis by regulating the function of HSCs and progenitor cells. An improved understanding of this regulation in homeostasis, ageing and cancer should aid the development of therapies to rejuvenate aged HSCs or niches and treat malignancies.
- Sandra Pinho
- Paul S. Frenette
Review Article11 Feb 2019 Nature Reviews Molecular Cell Biology
Autophagy as a promoter of longevity: insights from model organisms

Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, autophagy supports tissue and organismal fitness and promotes longevity. Thus, autophagy induction could be considered a strategy to extend lifespan.
- Malene Hansen
- David C. Rubinsztein
- David W. Walker
Review Article13 Jul 2018 Nature Reviews Molecular Cell Biology
Cellular and epigenetic drivers of stem cell ageing

Decline in stem cell function causes loss of tissue homeostasis and increased incidence of age-related diseases. During ageing, adult stem cells accumulate damage and the niche in which they reside malfunctions. These defects are associated with changes in the epigenome that contribute to organ dysfunction and disease.
- Maria Ermolaeva
- Francesco Neri
- K. Lenhard Rudolph
Review Article1 Jun 2018 Nature Reviews Molecular Cell Biology
The coming of age of chaperone-mediated autophagy

The selective degradation of cellular components via chaperone-mediated autophagy (CMA) functions to regulate a wide range of cellular processes, from metabolism to DNA repair and cellular reprogramming. Recent in vivo studies have enabled to dissect key roles of CMA in ageing and ageing-associated disorders such as cancer and neurodegeneration.
- Susmita Kaushik
- Ana Maria Cuervo
Review Article6 Apr 2018 Nature Reviews Molecular Cell Biology
Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

The majority of common diseases are associated with ageing. Diseases that cause premature ageing serve as natural model systems for studying the mechanisms of ageing and disease, as they share similar cellular and molecular hallmarks, including genomic instability, metabolic defects and loss of regenerative capacity.
- Nard Kubben
- Tom Misteli
Review Article9 Aug 2017 Nature Reviews Molecular Cell Biology

Molecular ageing

Reviews & Comments

FOXO transcription factors as mediators of stress adaptation

Ageing and rejuvenation of tissue stem cells and their niches

Molecular mechanisms of dietary restriction promoting health and longevity

NAD⁺ metabolism and its roles in cellular processes during ageing

Cellular senescence in ageing: from mechanisms to therapeutic opportunities

Old and new models for the study of human ageing

The ageing epigenome and its rejuvenation

mTOR at the nexus of nutrition, growth, ageing and disease

The roles of DNA, RNA and histone methylation in ageing and cancer

Decelerating ageing and biological clocks by autophagy

Cellular senescence causes ageing

The proteostasis network and its decline in ageing

Haematopoietic stem cell activity and interactions with the niche

Autophagy as a promoter of longevity: insights from model organisms

Cellular and epigenetic drivers of stem cell ageing

The coming of age of chaperone-mediated autophagy

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

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