Epigenetics of Aging

Edited by:
  • Trygve O. Tollefsbol
Springer: 2009. 448 pp. $199, £135 9781441906380 | ISBN: 978-1-4419-0638-0

Signs of ageing in animals originate from accumulated damage to the genome, proteins or corrupted cell components that reflect a decline in bodily maintenance. Others arise not from this primary damage, but through damage-limitation mechanisms that are provoked by cellular malfunctions. These frequently involve epigenetic processes — mechanisms that modify the information content of the genome without changing its DNA sequence.


Epigenetics of Aging, a collection of articles assembled by molecular biologist Trygve Tollefsbol, gives us a contemporary view of the epigenetic processes involved in ageing. The most significant of these, and the subject of several chapters, is the development of cellular senescence: a major reorientation of cell behaviour that becomes a formidable barrier to cancer.

Cellular senescence is a response to genomic damage and other insults, which activate the tumour suppressor proteins p16INK4a and p53 that promote DNA repair and stop cell division. The genome is then reorganized so that large regions form tight clumps in which genes that are normally active in cell proliferation are silenced. Senescent cells contribute to many characteristics of the ageing body, such as wrinkles.

The book explores a number of epigenetic mechanisms. However, by confining their scope to biochemistry, the authors divulge little of the recent progress in understanding the nature of senescent cells, from the ways in which they induce their neighbours to become senescent using secreted signals, to their capacity to remodel the cell interior and exterior — including loss of skin elasticity.

The book describes how, in the transition to senescence, the epigenetic role of Polycomb proteins — which sustain cell proliferation and repress differentiation genes — is abandoned. The sirtuins are another family of proteins with many epigenetic roles; by modifying the structure of histones and other proteins that are bound to DNA, they control how tightly clumped the genome becomes and facilitate DNA repair.

The advance of senescence is marked epigenetically by a steady loss of methyl groups from some genes and by sporadic gains of these groups in others. These random events can activate or suppress other genes. An important and intriguing contribution to the book shows that in humans, epigenetic markings change in response to life experience: by middle age, a cohort of identical twins developed diversity in their patterns of DNA methylation. This may be related to the variation in lifespan noted between identical twins.

Other articles link the loss of DNA methylation to the development of pathology, including the breakdown of cartilage in osteoarthritis and the production of the amyloid protein associated with Alzheimer's disease. The loss of methylation from critical genes impairs learning and memory function as studied at the cellular level. Several chapters reflect on the possibilities of finding pharmaceuticals that target epigenetic processes and which may be useful for delaying ageing or fighting cancer and other chronic conditions. However, that subject is in its infancy.

Surprisingly, the book ignores the vast body of work indicating that prenatal nutrition and other factors affect the prospects of the mammalian fetus through epigenetic mechanisms. A discussion of the consequences of the Dutch famine of 1944–45 would have been apposite: researchers have shown that, six decades on, children who were conceived during the Nazi-enforced famine suffered more cardiovascular disease and type 2 diabetes than a control group. This was linked to an undermethylated version of the gene for insulin-like growth factor 2. Another curious omission is any discussion of methylation and longevity in honeybees: the queen develops with an unmethylated genome and lives 20 times longer than a worker, whose genome is selectively silenced by methylation. There is more to the biochemistry of epigenetics than is recorded in this volume, including the role of poly(ADP-ribose) and chaperone proteins that help newly formed proteins fold into the correct shape and prevent the formation of toxic aggregates in cells.

Epigenetics of Aging reminds us that mysterious and fascinating processes govern the last phase of life in all organisms.