Can we delay aging?
Ninety percent of major diseases are related to aging; understanding the genetics of aging is key to a longer and healthier life
By David Levine Posted on 26 November 2013
Dr. Nir Barzilai has a sense of humor. In a recent forum for science journalists, he opened his talk by saying, "I am going to tell you how to die young at a very old age."
Dr. Barzilai, Director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the Glenn Center for the Biology of Human Aging at the Albert Einstein College of Medicine, was one of the panelists at a meeting sponsored by Science Writers in New York (SWINY) and the American Federation for Aging Research (AFAR) November 18 at the Cornell Club in New York City.
The program followed on the heels of a study in the October issue of Health Affairs, which found that research on aging delayed aging and age-related disease more effectively than disease-specific research while also saving money. In addition, Google recently announced the Calico initiative, which will focus on health and well-being, in particular the challenge of aging and associated diseases.
The biology of aging – and can we influence it?
The speakers were Ana Maria Cuervo, MD, PhD, Professor in the Departments of Developmental & Molecular Biology, Anatomy & Structural Biology and Medicine, and co-director, Einstein Institute for Aging Research, Albert Einstein College of Medicine; Nir Barzilai, MD, Director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the Glenn Center for the Biology of Human Aging at the Albert Einstein College of Medicine; and Caroline S. Blaum, MD, Director of the Division of Geriatrics at New York University's School of Medicine and Deputy Medical Officer of the American Federation for Aging Research (AFAR).
Dr. Barzilai's research is on key mechanisms in the biology of aging including the role of nutrients in extending life and the genetic determinants of lifespan. "Unless you delay aging," he said, "all you can do is trade one disease after another."
Dr. Barzilai was especially critical of cardiologists who focus on lower cholesterol with statins and without considering their neurological and long-term metabolic effects, such as diabetes.
Age is the major risk factor for Alzheimer's disease, cardiovascular disease and cancer. In essence, age is the major risk factor for death, but the medical system does not view age as a threat, instead treating one disease at a time.
Dr. Barzilai said there is good evidence for success in the goal of delaying aging. He observed that healthy lifespan has been extended in numerous animal models and that relevant drugs have been used in humans. He also noted that researchers are looking at not only the factors that cause longevity but why humans age at different rates.
He said the hypothesis that individuals who live longer have a "perfect genome" is not true. However, there is solid evidence that the hypothesis that people who live longer have protective genes that aid in their longevity is true.
"There is a remarkable family history of exceptional longevity in parents, siblings and offspring of centenarians," he said, referring to people who live to 100 or beyond. He showed a slide that showed that the offspring of centenarians were less likely to develop strokes, heart attacks or diabetes – all age-related illnesses – compared to the general population.
One would think that people who lived to 100 practiced healthier habits throughout their lives, such as more exercise, better diets and not smoking.
But this is not the case.
Dr. Barzilai said the studies of centenarians found that they don't eat any healthier or exercise more than people who die younger. "There is a compression of morbidity in centenarians," he explained. "The same diseases that affect people in their 80s don't develop in this group until later in life, and the span of the illnesses is shorter."
[caption align="alignright"]In his presentation, Dr. Barzilai said the hypothesis that individuals who live longer have a "perfect genome" is not true, but there is solid evidence they have protective genes that aid in their longevity. [/caption]
It is also less expensive to get sick later in life. According to the Centers for Disease Control and Prevention, the medical costs at the end of life for a person who is over 100 is $8,000. For a person 60 to 70, it is $24,000. This is known as the longevity dividend. (On November 22, AFAR and the Gerontological Society of America issued a new report, The Longevity Dividend: Geroscience Meets Geropolitics.)
Dr. Barzilai concluded his discussion with a brief overview of the research of genes and substances that may aid in longevity including resveratrol, rapamycin and cholesteryl ester transfer protein (CETP) inhibitors, which Merck is developing and Dr. Barzilai has been researching.
'The importance of keeping cells clean'
Dr. Ana Maria Cuervo, Professor in the departments of Developmental & Molecular Biology, Anatomy & Structural Biology, and Medicine, and co-director of the Institute for Aging Research at Albert Einstein College of Medicine, talked about the role of autophagy on aging.
Autophagy is a degradative process that helps balance the sources of energy at critical times in development and in response to nutrient stress. Dr. Cuervo is a leader in the study of protein degradation as it relates to the biology of aging, with an emphasis on neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's. She was recently asked by the National Institutes of Health to lead a panel on geroscience – the study of how aging influences the onset of chronic diseases.
Dr. Cuervo has published many papers on autophagy including Autophagy and Aging, Keeping that Old Broom Working and Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function, where she demonstrated that old mice cells become younger when autophagy is restored.
"Centenarians have the luck of having a system that cleans their cells better," she said. "For the rest of us, changes in lifestyle such as lowering the amount of fat and sugar in your diet and exercise are all known to increase cell cleaning among its benefits."
In that vein, she titled her presentation "Autophagy and Aging: the Importance of Keeping Cells Clean."
[caption align=alignright]Diseases such as Alzheimer's, Parkinson's and Huntington's all have in common the formation of "clumps" (aggregates) of abnormal proteins in the cells of the brain. In young individuals, cellular cleaning systems such as autophagy take care of continually eliminating these abnormal proteins, keeping cells healthy (top right). However, with age, the reduced activity of autophagy contributes to building up of these abnormal proteins that eventually intoxicate and kill the brain cells (bottom right). (Source: Ana Maria Cuervo, MD, PhD)[/caption]
One slide listed the many diseases hat are due to poor quality control. The list included Alzheimer's, Parkinson's and Huntington's — all age-related diseases of the brain. "There is a common basis for degeneration, and finding ways to delay or prevent degeneration will help people live longer and healthier lives," Dr. Cuervo said.
To understand the relation of aging and autophagy, she said, it is important to consider certain questions: Why does the cleaning system become less efficient as we age? What are the consequences of decreasing cell cleaning? And can we fix it?
She said her slide titled "Why Working on Garbage is so Interesting" describes her work well. "Getting rid of the garbage that accumulated in our cells helps to keep us healthy," she explained. "But this system breaks down as we age."
Dr. Cuervo said studies have shown that high-fat diets place an undue burden on the cell's cleaning system. But she noted that calorie restriction, which has been linked to longevity, has had mixed results in longevity studies.
'One of the biggest problems for my patients …'
Dr. Caroline S. Blaum is Director of the Division of Geriatrics at New York University's School of Medicine and deputy medical officer of AFAR. But she told the attendees she was speaking as a clinician.
Dr. Blaum is one of the nation's leading geriatricians and researchers on the care of the aged. She joined NYU last year from the University of Michigan to start the NYU Division of Geriatric Medicine and Palliative Care. Her research focuses on models of care, patients with complex health histories, frailty and diabetes in older adults. Blaum is involved in national efforts to redesign the way health care is delivered to the elderly.
For Dr. Blaum the investment in research on aging is both natural and important. "Older adults want to live to see their children and grandchildren live healthy and happy lives," she remarked.
She said our society needs to support research that focuses on the cumulative effects of disease:
Age is the number-one risk factor common to the major diseases. Our approach of treating one disease at a time doesn't work.
One of the biggest problems she sees among her own patients is polypharmacy.
"At any given time," she said, "an elderly patient takes, on average, four or five prescription drugs and two over-the-counter (OTC) medications. This puts elderly patients at risk for adverse reactions and makes it difficult for clinicians to get a clearer picture of what is going on with their patients."
Dr. Blaum said there are several factors that contribute to polypharmacy including the number of drugs available, the fact that patients see specialists, and that many drugs that were previously prescription only are now available OTC. "When you look at the prescriptions, OTC and alternative medicines an elderly patients takes, you see the need for coordination of care that will give patients the medications they need but avoid duplication and over-medication," Dr. Blaum said.
'What is the best way to prevent aging?'
In the discussion after the presentations, the panelists said research cuts are hurting not only our health goals but American's reputation.
Dr. Barzilai said he was concerned about the budget cuts to the NIH and the National Institute of Aging and the view of the FDA that aging is not an illness. He said, "The Europeans are pouring massive funding into research and working together to solve diseases as well as ways to delay aging. The US is being left behind."
[pullquote align="right"]The goal is to die young after living a very long life. That is what our research is all about. — Nir Barzilai, PhD [/pullquote]
The speakers also discussed how research on biological mechanisms of aging may have numerous practical benefits. "At the most basic level," said moderator Dr. Kevin Lee, "it may be providing mechanistic insights into the things our mothers told us — that exercise, eating well, getting adequate rest, and staying actively engaged are the keys to living healthier longer. Beyond that, the research has great promise for identifying novel targets for interventions to treat age-related disease."
One audience member asked, "What is the best way to prevent aging?"
Dr. Blaum said exercise and diet are important as they aid in the prevention of diabetes and other illnesses. "Exercise especially is the one thing you can do to slow down the effects of aging," she said.
Another audience member asked if there is an upper limit to how long we can live.
Dr. Barzilai said the panelists were not experts in this area, but to keep in mind that the goal is not how long you live but how well you live: "As I said earlier, the goal is to die young after living a very long life. That is what our research is all about."[divider]
David Levine (@Dlloydlevine) is co-chairman of Science Writers in New York and a member the National Association of Science Writers (NASW) and the Association of Healthcare Journalists. He served as Director of Media Relations at the American Cancer Society and as Senior Director of Communications at the NYC Health and Hospitals Corp. He has written for Scientific American. The Los Angeles Times, Good Housekeeping, BioTechniques, Robotic Trends and Nautilus and was a contributing editor at Physician's Weekly for 10 years. He has a BA and MA from The Johns Hopkins University.