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Friday, February 10, 2017

If telomeres could talk

One of the reasons cardiology tends to advance so rapidly compared to other medical disciplines, with very noteworthy benefits, such as marked declines in both premature death and disability related to heart disease, is because of the power of surrogate markers. Surrogate markers in medicine are generally things we can measure in the short term that tell us with at least reasonable, and sometimes excellent, fidelity about likely outcomes in the long term.

Cardiology's cup is full to the brim with good surrogate markers: LDL cholesterol, blood pressure, and heart rate for starters. In addition, there is coronary calcification scoring; lipoprotein(a); other lipids including HDL and triglycerides; CRP and other inflammatory markers; and stress testing for functional reserve. There is even an ultrasound method for direct conversations with blood vessels to ask them, in essence, “how's it going?” that provides a very robust indication of overall vascular health. We use this method, called endothelial function testing, in my lab, and have published many papers based on it over the years.

Those medical disciplines where surrogate markers are elusive have historically been held back as a result; cancer medicine is a good example. Oncology is advancing rapidly these days with new and powerful insights about immunology, but progress has lagged behind cardiology and endocrinology in part for want of markers that show in the short term if interventions can make cancer less likely in the long term.

Surrogate markers are powerful. When you show you can alter them meaningfully, you have good evidence you can change the outcomes that really matter-notably, vitality, and longevity.

Imagine, then, if we had a surrogate marker for life expectancy itself. Imagine how powerful it would be if something we could measure that changed rapidly in response to influences and stimuli, both good and bad, reliably predicted the length of healthy life. That would be quite a boon, since otherwise, the only way to show changes in the length of life would require waiting lifetimes. I suspect we can all agree it would be something of an anti-climax to learn only on your hundredth birthday that you were likely to live to 100.

It turns out, there is just such a surrogate marker for the length of healthy life. Telomeres are, structurally, caps at the ends of our chromosomes, they have been compared to the plastic caps at the ends of shoelaces. Health-promoting exposures, or alternatively the slings and arrows of outrageous fortune, can lengthen or shorten telomeres, respectively. The length of telomeres, in turn, predicts the length of life itself.

Not perfectly, of course; even with gloriously long telomeres, it would be imprudent to stand in the path of a moving train. But powerfully. Telomeres are among the most potent of known predictors of healthy life span, other things (like standing clear of trains) being equal. And, in fact, they are not just markers of health span, but actual mechanisms of it; vital telomeres transmit that vitality to the cells in which they reside. Imagine, then, how great it would be if we could talk directly to our telomeres, and find out how they're doing.

Now, we can. Hold that thought for just a moment and I'll get back to it.

First, I want to differentiate the value of surrogate markers from what we might call “duplicative markers.” Just because we can measure something doesn't mean there is always much value in doing so.

There is a famous expression that those who have a hammer tend to see nails, and the related idea that invention can be the mother of necessity. We tend to want to use whatever tools we happen to have.

In medicine, that at times means reliance on technology to tell us what we already know. Consider, for instance, the burgeoning array of studies using some cutting edge technology, like fMRI, to study brain responses to food.

You already know that when you eat, say, French fries, you experience intense but probably rather fleeting pleasure. You also know the various feelings that come after, from hunger to guilt. What, then, does a study showing that the pleasure center in your brain lights up when you eat those fries really teach us that we didn't already know? It's a bit like using high-tech thermal cameras to show that warm clothes keep you warm when you're out in the cold.

Do we really need cutting edge technology to show us changes in metabolic activity in the pleasure center of our brain to tell us we found something…pleasurable? Of course, other benefits may ensue from such research, but I do think it's worth noting that not every difference we can measure really makes much difference to what we know. Duplicative markers in medicine abound, and to me they often seem an excuse to spend a lot of money to corroborate what we already knew for free.

Surrogate markers are different, because they tell us something we otherwise couldn't know unless we waited for the outcomes they predict, and then , it would be too late. It's not helpful to find out after a heart attack that we are at risk for heart disease. It's even less helpful to find out after we die that our life expectancy isn't everything we might wish.

Which brings us back to telomeres. Their length is predictive of the length of healthy life, while providing the lead-time necessary to do something about it. If telomeres could talk, and tell us what makes them lengthen or shrink, what makes them happy or unhappy, they would provide us compelling, powerful, actionable intelligence and a measure of control over our longevity. Conversing with telomeres would be the next best thing to sipping from the fountain of youth.

And, as noted, we all have that opportunity now. In a newly released book called The Telomere Effect, two leading experts, one of them a Nobel Prize winner, go carefully through the science enumerating the effects of diverse exposures on telomere length. Drs. Elizabeth Blackburn and Elissa Epel proceed study by study, and cover everything from stress to diet, exercise to sleep, the influences of environment when we are just in the womb to those of social interactions throughout life. They then translate each cluster of studies into practical tips you can apply.

Of course, the lifestyle prescription that's good for our telomeres is one we already knew was good for us in general. But a vivid view of aging itself at the cellular level that does not require years and decades to elapse is a rarefied vista indeed, a truly unique window of opportunity. This book opens that window to us all.

If only telomeres could talk to us, they would provide unique insights into human aging, with the time to do something about it. It turns out they can, in the authoritative voices of Drs. Blackburn and Epel, on the pages of The Telomere Effect. Telomeres are talking now; I think everyone should listen.

David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his blog at The Huffington Post.

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Blog log

Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Auscultation
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Iowa City, IA, with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

DrDialogue
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

FutureDocs
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

KevinMD
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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