Translational geroscience: emphasizing function to achieve optimal longevity

Abstract

Among individuals, biological aging leads to cellular and organismal dysfunction and an increased risk of chronic degenerative diseases and disability. This sequence of events in combination with the projected increases in the number of older adults will result in a worldwide healthcare burden with dire consequences. Superimposed on this setting are the adults now reaching traditional retirement ages--the baby boomers--a group that wishes to remain active, productive and physically and cognitively fit as they grow older. Together, these conditions are producing an unprecedented demand for increased healthspan or what might be termed "optimal longevity"-to live long, but well. To meet this demand, investigators with interests in the biological aspects of aging from model organisms to human epidemiology (population aging) must work together within an interactive process that we describe astranslational geroscience. An essential goal of this new investigational platform should be the optimization and preservation of physiological function throughout the lifespan, including integrative physical and cognitive function, which would serve to increase healthspan, compress morbidity and disability into a shorter period of late-life, and help achieve optimal longevity. To most effectively utilize this new approach, we must rethink how investigators and administrators working at different levels of the translational research continuum communicate and collaborate with each other, how best to train the next generation of scientists in this new field, and how contemporary biological-biomedical aging research should be organized and funded.

Figure 1. Compressing morbidity by slowing the processes of aging

Slowing the fundamental biological processes of aging as a tactic for achieving delaying the age of onset of multiple co-morbidities, as opposed to preventing or treating individual age-associated clinical disorders.

Figure 2. Increasing healthspan and optimal longevity

Comparison of current vs. ideal healthspan. Extending healthspan is a critical component of achieving optimal longevity, defined as living long, but with good health, function, productivity and independence.

Figure 3. Translational geroscience

Translational gero-science represents an integrative model for conducting biological-biomedical aging research leveraging a bi-directional, continuum of observations from basic science to populations using multidisciplinary approaches.

Figure 4. Role of preserved function in achieving optimal longevity

Maintenance of good physiological function with aging delays the onset of chronic diseases and disability, increases healthspan, compresses morbidity, extends mean lifespan and helps attain optimal longevity.

Figure 5. Compression of physiological dysfunction with aging

Compression of physiological dysfunction (or rectan-gularization of function) with aging would allow function to be well maintained with advancing age, limiting the occurrence of major functional limitations to a period near the end of life, thus enhancing healthspan.

Figure 6. Sources of new treatments for slowing effects of aging

Sources of new treatments for slowing the fundamental processes of aging include newly developed prescription agents, repurposed FDA approved drugs, novel lifestyle behaviors (e.g., intermittent fasting) and nutraceuticals (dietary supplements, medical foods and functional foods).

Figure 7. Key components of translational geroscience

Essential elements required for successfully conducting future translational geroscience research include effective communication, collaboration, funding sources, infrastructure and career development mechanisms. ITP, Interventions Testing Program; TTP, Translational Testing Program.