Fight Aging!

This open access paper is quite representative of attitudes in much of the aging research community. Scientists are excited by the obvious burst of progress and possibilities, and changing attitudes in the research community let them openly express the desire to intervene in the aging process without risk to their careers - a concern that significantly suppressed dialog on treating aging as recently as a decade ago. Yet at the same time, very few people look past the established approach of drug development to tinker with metabolism in the hope of slightly slowing the aging process, and that is certainly the case here. The SENS rejuvenation research approach of repairing the cell and tissue damage that causes aging in order to reverse the aging process still has a long way to go in order to capture even a sizable fraction of the mainstream and its funding. This is why advocacy and philanthropic fundraising remain very important.

We are at a tipping point in the biology of aging-from lifespan extension per se to maintaining and extending health in late life. Since the early 1980s, there have been serious efforts to use genetic approaches to extend lifespan in model systems such as Caenorhabditis elegans, Drosophila, and, increasingly, mice. Collectively, such efforts fall under the catch-all term "geroscience", which describes interdisciplinary efforts to better understand the biology of aging with a view towards improving healthcare in the elderly. Recently, the tried and true genetic approaches of the 1990s and early 2000s in geroscience research have been increasingly giving way to a plethora of pharmacological approaches to extend lifespan. This has been in conjunction with efforts to simultaneously increase healthspan, thereby providing a preclinical rationale for similar studies in human beings.

It has been reported that lifespan and healthspan can be extended in invertebrates using a variety of pharmacological approaches, including single antioxidants through small molecule screens and natural compounds as well as some anticonvulsants. Not to be outdone, there are also supporting data for lifespan/healthspan extension in mice using repurposed US Food and Drug Administration (FDA)-approved drugs, novel chemical compounds, and biologicals. Before examining key concepts in geroscience that drive a lot of the excitement in the pharmacology of lifespan/healthspan extension, it is necessary to first of all define what we mean by aging and healthspan. This is particularly germane in the model systems most commonly used in the biology of aging. By no means is the definition of such terms straightforward, and eminent figures in the field have spent considerable effort clarifying such apparently simple concepts. For the purposes of this article, the term "aging" refers to post-reproductive changes that adversely affect lifespan. However, to define healthspan in the context of geroscience is perhaps even more difficult.

Healthspan is commonly interpreted to mean "maintenance of functional health with increasing age". By necessity, this means one has to understand what it is to be healthy for multiple different systems and tissues. In human beings, this is perhaps non-controversial-one can access high-quality data collected from many thousands of individuals of both sexes as well as differing ethnicities while controlling for multiple lifestyles. One can then establish age-dependent measures for many different aspects of human biology. These include measures of cardiovascular and cognitive function, movement (walking speed), renal function, and hemodynamic function, to name a few. Typically, such functional measures peak in early adulthood, then decline at different trajectories as the individual ages. There are many factors that can modulate the slope of such a functional decline with age, including exercise, diet, and lifestyle. Maintaining function and independence with age using selective and specific interventions is arguably the single biggest challenge currently facing geroscience. For the model systems commonly employed in the study of aging biology, identifying functional measures that are relevant to human healthspan is quite difficult. In nearly all model systems used in the biology of aging, healthspan measures have been collected from aging animals not necessarily because of their relevance to human aging but because methods exist that allow one to measure the metric in question over time. Amongst these metrics, there is one clear measure that is very well established as being a robust biomarker of healthspan in human aging, and that is the measurement of movement with age. A sound argument can be made for measuring this parameter in model systems of aging to ensure potential translational relevance.