MITOCHONDRIAL DNA MUTATIONS IN AGING, DISEASE AND CANCER

JOURNAL OF ANTI-AGING MEDICINEVolume 1, Number 4, 1998Mary Ann Liebert Inc.

Book Review

MITOCHONDRIAL DNA MUTATIONS INAGING, DISEASE AND CANCER.Keshav K. Singh (ed.), $175.00. Springer Ver¬lag: Heidelberg, Germany, 1998, 412 pages

This book is a comprehensive and up-to-datesurvey of our knowledge of mitochondria

with each chapter written by foremost special¬ists in its area. The subjects covered include notonly the three mentioned in the title but alsomitochondrial structure, function, genetics andinheritance. There is even a chapter about theeffects of mitochondrial DNA mutations inplants. Of its 20 chapters, only one is explicitlyconcerned with the relevance of mitochondrialDNA mutations to aging.Far frombeing a reason for readers of this Jour¬

nal to ignore this book, however, this is a strongpoint in its favor. Perhaps regrettably, it is in thenature of biology that one must master a fear¬some quantity ofbackground information beforeone can reallymake sense of a research area. Thisis, arguably, truer in gerontology than in anyother biological field. For a reader whose maininterest is in aging, disease and/or cancer, sevenof the first eight chapters might reasonably besummarized as background material, since theydescribe aspects of mitochondria whose DNAhas not suffered mutations; but, without an un¬

derstanding of them, it is impossible to gain an

in-depth appreciation of what goes wrong whenamutation occurs. Moreover, there remainmanyopen questions concerning normal mitochon¬dria,which these "background" chapters discussin commendable detail.Mitochondrial mutations have long been

known to cause severe pathologies at an earlyage, as well as possibly being involved in "nor¬mal" aging. Though the clinical symptoms ofthese early-onset diseases do not resemble "ac¬celerated aging" to the same degree as those ofsome diseases caused by nuclear mutations,there are many similarities at the subcellularlevel which bring such diseases to the attentionof the gerontologist. These diseases are dis¬

cussed at length. Further chapters are dedi¬cated to the evidence implicating mitochondr¬ial DNA mutations in some much commoner,late-onset pathologies: neurodegenerative dis¬eases and cancer each occupy a chapter.Finally there are three chapters focusing on

treatment of maladies caused by mitochon¬drial DNA mutations. Two of them are specificto cancer; the third—the last chapter in thisbook—discusses gene therapy, and is thus po¬tentially relevant to all the effects that such mu¬tations may have. I found it the only disappoint¬ing chapter in the book. There are three majorstrategies for the development of mitochondrialgene therapy, all being actively pursued; expertopinion is very divided with regard to which ofthem will turn out to be most feasible and effec¬tive. It is therefore natural for reviews of this areato express an opinion on that matter, but it is im¬perative that the approaches which the authorsdo not favor should be given careful considera¬tion. Here, however, one of themajor strategies—introduction of copies of 13 mitochondrial genesinto the nucleus, with modifications so that theencoded proteins will be imported back into mi¬tochondria—is dismissed mainly on the basis ofan argument whose error any high school biol¬ogy student should be able to spot,while thewell-known genuine obstacle to it—these proteins'huge hydrophobicity, which impedes their im¬port—is not mentioned at all. Such cursory ex¬amination of competing ideas is regrettable.A more general criticism of this book is one

that applies to the large majority of reviews ingerontology: many chapters would have bene-fitted from concluding with more courageousspeculation regarding mechanisms. Overall,however, this is a highly valuable overview ofcurrent knowledge (and ignorance) in all ma¬jor areas relating to mitochondrial DNA muta¬tions in aging and related pathologies.

Aubrey D.N.J. de GreyUniversity of Cambridge

E-mail: ag24@gen.cam.ac.uk369