Delayed ageing through damage protection by the Arf/p53 pathway.
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.
Matheu
Ander
A
Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Maraver
Antonio
A
Klatt
Peter
P
Flores
Ignacio
I
Garcia-Cao
Isabel
I
Borras
Consuelo
C
Flores
Juana M
JM
Viña
Jose
J
Blasco
Maria A
MA
Serrano
Manuel
M
D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D005347:Fibroblasts; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53