The common biology of cancer and ageing : Article : Nature

At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic— and some say unethical—events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer. Like so many areas of science, our subject is one that has no true beginning, and as yet, no clear ending. However, if we must begin somewhere, it would be in the winter of 1951, when a 31-yr-old woman and mother of five small children underwent a seemingly routine biopsy for a suspicious cervical mass. A portion of that biopsy went as usual to the pathology lab for diagnosis; unbeknownst to the patient, another portion was diverted to the research laboratory of two investigators at Johns Hopkins, George and Martha Gey. The Geys had spent the better part of the preceding twenty years attempting to find a human cell that could grow indefinitely in laboratory culture conditions. That search would end with the arrival of this particular biopsy sample. Unfortunately for the patient, the pathology laboratory quickly confirmed that the mass was indeed cancer and, despite surgery and radium treatment, the patient succumbed to her disease a mere eight months later. On the day of her death, in October 1951, George Gey appeared on national television in the United States to announce that a new era in medical research had begun. For the first time, he explained, it was now possible to grow human cells continuously in the laboratory. He termed the cell line he had created the 'HeLa cell', in memory of Henrietta Lacks, the unfortunate young mother whose biopsy sample made all this possible. Over the next 50 years, researchers would slowly strip away many of the secrets of how a cancer cell achieves and maintains its immortality. Here we review those efforts in an attempt to give both a historical perspective and an update on the more recent experimental highlights. In particular, we will focus on five aspects of cancer biology that appear to be particularly informative about normal ageing: the connection between cellular senescence and tumour formation; the common role of genomic instability; the biology of the telomere; the emerging importance of autophagy in both cancer and ageing; and the central roles of mitochondrial metabolism and energetic-dependent signal transduction in both processes. Together, these findings seem to indicate that both cancer and ageing represent complex biological tapestries that are often—but not always—woven by similar molecular threads.