Friday, 11 March 2011

Aging and the Heart: A Post-Genomic View

Aging and the Heart: A Post-Genomic View
José Marín-García | 2007-12-19 00:00:00 | Springer | 574 | Internal Medicine

In this book, the genetic and molecular basis of cardiovascular aging is examined in detail and a comprehensive assessment given of the bioenergetics changes occurring in human and animal models of cardiac aging. Both current diagnostic and future therapeutic modalities are presented, giving this book a dual-pronged approach. Cardiac aging, like aging in general, is a complex process involving numerous cellular and molecular changes. This book sheds new light on the phenomenon.


By Jose' Marín-García

The heart is a tough organ: a marvelous mechanism that, mostly without

repairs, will give valiant pumping service up to a hundred years.

Willis John Potts, MD, American surgeon, 1895-1968


from time immemorial. Although one cannot live as a perpetual

young person, in recent years there has been tremendous

interest in prolonging duration or longevity, with the

necessary caveat of preserving the quality of life. Antiaging

(looking younger) and longevity (living longer) are 2 common

contemporary themes in popular culture. Now that the

Human Genome Project (a global 15-year initiative culminating

in 2003) is completed and there has been an ongoing

research initiative in molecular cardiology, the quest for

understanding the scientific mechanism of general aging--

particularly cardiac aging--has commenced.

The human genome comprises 20 000 to 25 000 proteincoding

genes in the chromosome and is composed of more

than 3 billion nucleotides. The implications of these developments

can potentially be revolutionary, eg, they could lead

to increased availability of genetic testing for gene-related

medical disorders and interventional genetic therapy (gene

engineering) to avoid or minimize these conditions in offspring.

Numerous biotechnology methods, including proteomics

(which applies the techniques of molecular biology,

biochemistry, and genetics to analyze the structure,

function, and interactions of the proteins produced by the

genes) and recombinantDNAand other techniques, are being

used to study the structural and functional changes in cardiac

cells in several pathologic states as well as in aging, both

general and cardiac.

Jose' Marín-García, director of the Molecular Cardiology

and Neuromuscular Institute in Highland Park, New

Jersey, and author of Aging and the Heart, has written

a comprehensive and authoritative book about cardiac

senescence in the postgenomic period. The book deals

with a complex issue and, though lucidly written, is necessarily

a highly technical text, particularly for the nongeneticist.

While the average life expectancy in the United States was

a mere 47.3 years in 1900, it had increased to 77.9 years by

2004 and is expected to further increase to 79.2 years by

2015, thanks to improved health care, nutrition, and standard

of living, as well as lifestyle changes. Age-dependent

degenerative changes with anatomical and functional derangements

in cells, leading to cardiovascular disease, osteoporosis,

malignancy, degenerative joint disease, dementia,

and diabetes and other disorders, compromise quality

of life in aging populations.

Theories of general and inevitable aging are thoroughly

discussed in the first chapter; aging of the human heart and

vasculature is then tackled in subsequent chapters. A unique

feature is the summary bullet points section at the end of

most chapters, following the "Conclusion" section and enumerating

the salient and important points to remember.

Novel genes can be introduced into cardiac cells using

several vectors, including viral constructs and DNAcontaining

plasmids. Stem cells from embryos and adults

have been implanted in the defective myocardium to

enhance repair and improve contractility. These stem

cells include adult cardiac stem cells and endothelial progenitor

cells, which are diminished with senescence and

can potentially play a reparative and regenerative role in

various cardiac pathologies. Other emerging therapeutic

modalities include individualized drug therapy and use of

nutrients based on genomics (eg, nutrigenomics and


A tantalizing prospect in the near future is "personalized"

medicine, which will take into account the molecular

understanding of disease based on a person's unique clinical,

genetic (DNA-based), genomic, and environmental information

and thus optimize preventive strategies including

drug therapy on a proactive level and in a customized

fashion. At the core of personalized medicine lies the information

gathered through a comprehensive data set derived

through the disciplines of genomics (sequence of human

genome), transcriptomics (gene expression profiles), proteomics

(protein expression assay), and metabolomics--

also called metabonomics (assay of metabolic derangements)

--all of which will help in devising methods for

individualized care.

The last chapter, "Aging and the Frontier Ahead," finishes

on an optimistic and positive note with the suggestion

that "possible reversal and/or retardation in aging and

perhaps more importantly more effective treatment of agingassociated

diseases may become a reality within the next decade

or two."

The book is extensively referenced and thoroughly

researched. The bibliographies provided after each chapter

are exhaustive, and the end of the book includes an

ample glossary section defining the plethora of acronyms

used throughout. Despite being highly technical and

using special genetics terminology, the book is a good

read that deals with an exciting new chapter in the annals

of scientific exploration that potentially can have an

epoch-making impact on human longevity and better cardiac

health. As stated in a quotation mentioned by the

author in the book's preface, "Time will pass, inevitably/

Death will follow, consequently/After a healthy and productive

aging, hopefully."

M. Saleem Seyal, MD

River Cities Cardiology

Jeffersonville, Indiana


©2008 American Medical Association. All rights reserved. (Reprinted) JAMA, September 3, 2008--Vol 300, No. 9 1083

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