Recent breakthroughs in ageing research have shown that it is possible to slow ageing and extend the healthy lifespan of laboratory animals.
Whether the motivation is to find a pill that extends life span or just the curiosity to understand how and why we age, the science of ageing has grown in molecular detail. It is now becoming clear that changes at the levels of DNA, protein, cells and tissues all contribute to organismal ageing. Intriguingly, despite the diverse inputs, there are some common molecular themes and a few pathways and genes that have emerged as important modulators of ageing. All of these topics, and more, are represented in this Web Focus, which accompanies the September 2007 Focus issue of Nature Reviews Molecular Cell Biology, providing a snapshot of this exciting and fast-moving field.
Experts Lenny Guarente, Cynthia Kenyon and David Sinclair discuss the promise and the challenges of this fast-moving field in the accompanying Podcast, which was produced with support from Sirtris Pharmaceuticals.
Research Highlights
Ageing: A new player in the old game
doi:10.1038/nrm2250
Nature Reviews Molecular Cell Biology 8, 675
Ageing: Getting old and cancer: hand-in-hand?
doi:10.1038/nrm2247
Nature Reviews Molecular Cell Biology 8, 676
In Brief: Ageing
doi:10.1038/nrm2252
Nature Reviews Molecular Cell Biology 8, 676
Reviews
Progeria syndromes and ageing: what is the connection?
Christopher R. Burtner & Brian K. Kennedy
doi:10.1038/nrm2944
Nature Reviews Molecular Cell Biology 11, 567-578
Despite decades of research, the extent to which human progerias resemble accelerated ageing is still unclear and highly debated. Understanding this connection will require the ongoing characterization of genetic pathways that influence the ageing process in model systems and investigations into molecular pathways that define the pathogenesis of human progerias.
Endocrine regulation of ageing
Steven J. Russell & C. Ronald Kahn
doi:10.1038/nrm2234
Nature Reviews Molecular Cell Biology 8, 681-691
Mutations in genes that regulate endocrine signalling pathways can increase the lifespans of worms, flies and mammals. Endocrine pathways might therefore serve as targets for the manipulation of the ageing process and prevention of age-related diseases.
The role of nuclear architecture in genomic instability and ageing
Philipp Oberdoerffer & David A. Sinclair
doi:10.1038/nrm2238
Nature Reviews Molecular Cell Biology 8, 692-702
Changes in nuclear architecture are a hallmark of ageing in yeast and mammals. These changes seem to be driven by DNA damage, which results in age-related alterations in gene expression, and may be a conserved cause of ageing.
How stem cells age and why this makes us grow old
Norman E. Sharpless & Ronald A. DePinho
doi:10.1038/nrm2241
Nature Reviews Molecular Cell Biology 8, 703-713
Evidence from rodent and human experimental studies supports the view that a decline in the regenerative function of stem cells with age contributes to mammalian ageing and, possibly, several age-associated diseases. However, a few crucial questions remain to be resolved.
Perspectives
Opinion
Cancer and ageing: convergent and divergent mechanisms
Manuel Serrano & Maria A. Blasco
doi:10.1038/nrm2242
Nature Reviews Molecular Cell Biology 8, 715-722
Convergent mechanisms limit the amount of cellular damage and thereby protect against both cancer and ageing, whereas divergent mechanisms prevent excessive proliferation and, therefore, prevent cancer but promote ageing. The net balance between these mechanisms ensures a healthy, cancer-free lifespan until late adulthood in most individuals.
Opinion
Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?
Marco Giorgio, Mirella Trinei, Enrica Migliaccio & Pier Giuseppe Pelicci
doi:10.1038/nrm2240
Nature Reviews Molecular Cell Biology 8, 722-728
According to the free-radical theory, oxidizing species — including hydrogen peroxide (H2O2) — are generated during aerobic respiration and cause molecular damage and ageing. However, recent evidence suggests that H2O2 that is produced as a signalling molecule by a selected genetic programme regulates ageing.
© 2018 Macmillan Publishers Limited, part of Springer Nature. All Rights Reserved.
