US Senate Special Committee on Aging: Why Research Collaborations Matter
Before the break the United States Senate Special Committee on Aging held a roundtable event: Tackling Diseases of Aging: Why Research Collaboration Matters. The purpose is to explore what it takes to create treatments for chronic diseases that affect the elderly.
Video of the event can be found here. Roundtable witnesses widely agreed that industry collaboration with researchers is crucial to address health policy challenges facing an aging population.
Chairman Senators Bill Nelson (D-FL) and Ranking Member Susan M. Collins (R-ME) convened the event.
Witnesses included: Richard Hodes, MD and Director of the National Institute on Aging at the National Institutes of Health; John Alam, MD and Head of the Therapeutic Strategic Area for Diseases of Aging at Sanofi-Aventis; James Kirkland, MD, PhD and Professor and the Noaber Foundation Professor of Aging Research and Director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic.
Other witnesses: Richard Morimoto, PhD and Professor in the Department of Molecular Biosciences and Director of the Rice Institute for Biomedical Research at Northwestern University; David Morgan, PhD, Chief Executive Officer and Director of the Byrd Alzheimer Institute and Director of Neuroscience Research at the University of South Florida College of Medicine.
The event's moderator was Michael Hodin, PhD and Executive Director, Global Coalition on Aging and Managing Partner at the High Lantern Group.
Selected highlights from the event's witnesses:
Richard Hodes, MD and Director of the National Institute on Aging at the National Institutes of Health:
[A]fter about age 65, people become increasingly susceptible to progressive declines in physical and mental abilities. Age is well established as a primary risk factor for many disabling diseases and conditions, and even today, recent demographic studies are beginning to show increases in activity limitations among members of the enormous baby boom cohort. For this reason, the development of new interventions to improve and maintain health into old age – to improve healthspan– is an increasingly urgent frontier for modern medicine.
Since its inception in 1974, the NIA has supported groundbreaking research on the basic biology of aging in research laboratories around the country and within our own Intramural Research Program.
Exciting findings from NIH's ongoing support of studies in the basic biology are suggesting new avenues for the development of interventions for age-related diseases and conditions, some of which are described in this summary. Some of the latest findings are described here. Until recently, the study of the fundamental processes that underlie aging has often been dissociated from clinical work on aging- related disease and disability. In an attempt to bridge this gap, researchers have established the emerging field of geroscience, which is focused on the mechanisms by which the basic biology of aging drives chronic disease.
As you have heard, NIH's GeroScience Interest Group (GSIG) promotes innovative approaches to increase our understanding of the relationships between the biological processes of aging and age- related chronic diseases and disabilities. Established in 2011, the GSIG currently includes members from over 20 NIH Institutes and Centers and is one of the fastest growing Interest Groups at NIH – a testament to both the high level of cross-disciplinary interest in the topic and its critical importance with respect to public health.
The GSIG and its partners, the Gerontological Society of America and the Alliance for Aging Research, presented a historic summit on "Advances in Geroscience: Impact on Healthspan and Chronic Disease." Over 50 leading geroscientists will participate, and more than 500 attendees have registered to join. Discussion and deliberation at the Summit generated research recommendations that will advance this critical area of science.
John Alam, MD and Head of the Therapeutic Strategic Area for Diseases of Aging at Sanofi-Aventis:
Historically, the industry has been most successful in discovering and developing medicines for either acute illness, such as bacterial and viral infections, and cancer; or major chronic illness that strikes otherwise healthy younger middle-aged individuals, such as heart disease, autoimmune diseases (e.g. multiple sclerosis, rheumatoid arthritis) and diabetes. In such contexts, because there are high levels of physiologic distinction between health and disease, science has been able to develop models defining that distinction and uncover biologic pathways whose modulation specifically addresses the disease state.
In contrast, with perhaps the exception of chronic cardiovascular disease, the industry and biomedical research generally has been less successful in developing appropriate models and new medicines for most of the chronic diseases of aging. In many of the conditions, while symptomatic therapies have been developed, medicines that address the underlying cause of such diseases and conditions remain elusive. As a result, patients continue to develop increasing disability and morbidity, while incurring ever more health care costs.
The major scientific challenge posed by chronic diseases of aging and the geriatric syndromes is that the distinction between what would be considered "normal" aging and disease are less clear because more complex, than with acute illnesses of younger populations; often subtle dysfunctions accumulate in each of multiple organ systems leading to decreased autonomy and lack of well-being on the part of an individual patient. This is particularly true of geriatric syndromes such as Frailty, where various combinations of disease and aging processes come together to lead to an overall decline in function.
Indeed the treatment and management of geriatric syndromes is a challenge for medicine overall as no one abnormality drives the physical complaint, and as a result no one treatment is able to address the medical problem; instead, often frail individuals are treated with multiple medications that treat each of the individually identified laboratory abnormalities, but the underlying conditions of aging and physical frailty remains unaddressed. For pharmaceutical R&D the challenge that is posed by these subtle changes and the overlap between normal aging and disease is that it is scientifically difficult to define and model the specific biologic mechanism that is aberrant and therefore to find a medicine that specifically addresses the mechanisms causing the medical condition.
James Kirkland, MD, PhD and Professor and the Noaber Foundation Professor of Aging Research and Director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic:
Research in aging and clinical care for older patients is best pursued using interdisciplinary approaches. Therefore, we feel that creation of initiatives across departments within our own institution and among aging centers nationally and internationally could help to accelerate discovery and implementation of interventions to enhance healthspan and quality of life. The GSIG initiative at NIH is based on the same principles and has helped to guide the types of collaborative efforts within and among institutions that are necessary for development and implementation of interventions to enhance healthspan and delay, prevent, or treat age- related chronic diseases. Tomorrow's interdisciplinary summit in Bethesda entitled Advances in Geroscience: Impact on Healthspan and Chronic Disease exemplifies these efforts.
In summary, the aging field is at an exciting juncture, with recent discoveries of interventions that hold potential for increasing healthspan and lifespan and combating major age-related chronic diseases as a group, instead of one at a time. While by no means fully certain, it appears increasingly likely that some of these interventions may soon be ready to be tested in clinical trials. There is enough promise now that a major initiative to accelerate this work is warranted.
Clinical translational research is expensive and is a new area within the aging field. It needs to be supported without cannibalizing discovery and hypothesis-driven research in the aging field. Support for these areas is already meager and must be sustained or increased to maintain or expand the discovery pipeline, so new and better interventions can continue to be devised.
We in the aging research and clinical care community are doing our best with what we currently have. We are coordinating efforts among and within our academic institutions, setting priorities to advance basic and clinical research, creating stronger links between scientists and clinicians, including not only those studying aging mechanisms, but also individual age-related diseases, and developing training programs and curricula to create the new breed of clinician- scientists in aging research who will be needed as translation progresses and clinical trials begin.
More could be done, and hopefully will be, as these steps are taken and increased funding allows us to move faster in this area. We are optimistic that support might increase as the potential benefits of targeting age-related diseases as a group and enhancing healthspan are recognized by the public, governments, donors, industry, and our colleagues across scientific and clinical disciplines.
Since the first wave of baby boomers started turning 65 in 2011 and 11,000 people per day will continue to reach this milestone until 2030, the potential gains for society with this approach are substantial, possibly even transformative.
Richard Morimoto, PhD and Professor in the Department of Molecular Biosciences and Director of the Rice Institute for Biomedical Research at Northwestern University:
Aging is the common platform for all of biology and the basis for all degenerative diseases. By mid-century in the percentage of Americans over 65 will have grown substantially as we join Japan, Germany, France, Italy, Britain, and most of Europe. With this demographic shift will be the inevitable explosion in neurodegenerative diseases, dementia, cancer, and metabolic diseases such as adult onset diabetes.
The problem facing us is clear, without new drugs or treatments for age-associated degenerative diseases, why would anyone want to know that they are at risk. While at the same time, it will be essential to have biomarkers that detect changes in quality control that predict enhanced risk for age-associated disease. Either alone will be insufficient, so we must find ways to advance both approaches simultaneously.
The adult organism is mostly about replacing its parts as each component wears out. However, unlike the pyramids, the Golden Gate Bridge, or even a fine Swiss watch, biology does not use inert parts. Rather, in biology the replacement parts are transient in nature and often imperfect, and most often they are just good enough.
Consequently, all biological systems decline with age, and eventually the system (the body) breaks down. Despite this, there is hope as humans are living longer. But will this be useful and productive if living longer is not living healthy lives? Of what value to society will be a lifespan of over 100 years if the body begins to fail three decades earlier?
Therefore, rather than to wait until disease is evident, which is the current state of medical affairs, we must identify the earliest markers of quality control collapse, when the cell stress response has been pushed beyond its capacity and can no longer protect the cell against damage. Only then, perhaps years if not decades before the inevitable decline can we promote an alternative path, towards healthy aging.
Research on the biology of aging is therefore the base of knowledge onto which we can understand the course of life and transitions from apparent health through aging to disease. An understanding of how cells and animals maintain their robustness, to identify the genes and networks that maintain balance, and how these stress response systems get overwhelmed and become dysfunctional will be invaluable to both health and disease.
To accomplish this task will require new investments and new teams. Moreover, these teams should represent new partnerships of academic and industrial researchers working towards a new goal that is not necessarily to cure any particular disease.
David Morgan, PhD, Chief Executive Officer and Director of the Byrd Alzheimer Institute and Director of Neuroscience Research at the University of South Florida College of Medicine:
Is NIH funding initiatives for the delayed aging model? Yes. I presently serve on a review committee for the Interventional Testing Program to identify agents that can be administered which might extend the lifespan of mice. This is a very rigorous program that has identified one agent, rapamycin that can extend longevity. On this basis it is argued that this slows the aging process. Over 20 other agents have completed testing or are in process.
This is a highly objective means to try and identify chemoprevention for aging. However, expanding to other species that may have causes of death different than those of mice would seem a good use of funds. Research on caloric restriction and caloric restriction mimetics continues to receive such funding. Unfortunately, the studies in nonhuman primates had inconsistent outcomes, and these were long and expensive research studies. This leaves open the question regarding caloric restriction and longevity in humans.
How would NIH consider partnership with industry? Most certainly it would. A fine example of the government, industry and private philanthropic partnership is the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Almost 1000 publications have come from the data collected in this very large multicenter study. This is an example of the "precompetitive " research space, where the pharmaceutical industry sees that all can gain benefit before competing with specific proprietary drugs. These are ideal relationships.
Michael Hodin, PhD and Executive Director, Global Coalition on Aging and Managing Partner at the High Lantern Group:
[P]opulation aging prompts questions that are far more fundamental than how to increase funding for this disease or that entitlement program. Indeed, population aging demands a fresh, innovative approach to policymaking where the incompatibility between 20th-century approaches and 21st-century demographic realities is fundamentally challenged.
But I am optimistic that we Americans actually know how to do this; to take huge challenges and find real solutions. Let me suggest three models that have been the basis for wealth creation and prosperity and driven by our unique sense of American optimism. They are models for how we can view today's challenge of population aging.
The first is the creation of the national interstate highway network in the mid-20th century. American leaders recognized that investing in highways would connect regional economies to spur national economic synergy, and a federal-state partnership was formed to undertake the project.
Despite plenty of political wrangling, the transcontinental network was built, and it laid the foundation for national economic development unparalleled before or since. It did not have to be. Yet it was done – and done in a way that connected excellent execution, vision, good ideas and ideals. We are better off as a nation for it. And, at its core, it happened through a deep understanding that spending on new transformative ideas should be viewed not as a cost but as an investment in our future – and that the price of not investing is far greater than the reverse. In its implementation it also showed what can be achieved through a comprehensive and integrated approach to public policy that broke down silos and generated cooperation, collaboration and excellence.
My esteemed colleagues today will talk a great deal about this need of silo-busting and more comprehensive approaches for our research into the diseases of aging.