Aging and the Heart—A Post-Genomic View

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

The quest for the fountain of youth has continued 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 protein-coding 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 recombinant DNA and 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.

José 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 DNA-containing 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 pharmacogenomics).

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 aging-associated 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.”