These last few years have seen a shift in

These last few years have seen a shift in emphasis from the investigation of individual age-related diseases in isolation toward a broader context to define the basic biology of aging. The concept behind the recently coined pursuit of GeroScience (Burch et al., 2014) is that a strategy to delay the aging process itself would decrease vulnerability across the age-related disease spectrum leading to lower morbidity and comorbidity. Indeed the concept that aging might be a suitable drug target in a clinical context is gaining traction and there is considerable effort being applied to bring this methylphenidate hcl idea to fruition (Longo et al., 2015). One of the most valuable tools in aging research is caloric restriction (CR), a proven intervention to delay aging and age-related disease (Fig. 1). If we could understand what mechanisms are employed by CR to impinge on the aging process we could potentially identify causal networks that contribute to the increase in disease vulnerability as a function of normative aging.
Human Aging Studies Several large-scale longitudinal aging studies have contributed enormously to our current understanding of the physiological changes during aging and their impact on health in old age. The Baltimore Longitudinal Study of Aging started in 1958, even before the foundation of the National Institute on Aging NIA in 1974. The study set out to determine the trajectory of change as a function of normal aging. Over the years 1300 participants have been monitored longitudinally, with health, cognitive and functional assessments conducted periodically. More recently, auxiliary studies have been conducted to identify the molecular signature of age related functional declines, including the investigation of the ability of biological markers such as serum metabolites to index physical function (Moaddel et al., 2016). Studies such as these will contribute new biomarkers with utility for diagnosis and treatment efficacy monitoring but also have potential to reveal the underlying biology of the age-related disorders. The Health Aging and Body Composition (Health ABC) is a longitudinal study of over 3000 subjects in the 70–79year old age range that were recruited in 1997 and followed for a decade and a half. Data from this study have featured in hundreds of publications since 1999. Early reports focused on functional decline with age (Simonsick et al., 2001) but as the study progressed reports of interactions among measured parameters and their association with disease have emerged (Beavers et al., 2013). The survey of Midlife Development in the US (MIDUS) was launched in 1995 with the overarching goal to discover the contributions of behavioral, psychological, and social factors to variation in health and well-being as a function of age (Radler, 2014). A repository of data and specimens collected from subjects in the study has enabled the investigation of biological factors to determine how these impact aging and health, such as interactions among biological indices as predictors of health and the role of inflammatory tone (Elliot and Chapman, 2016). The Wisconsin Longitudinal Study is a long-term study of a random sample of 10,317 men and women deciduous graduated from Wisconsin high schools in 1957 (Herd et al., 2014). Survey data were collected from the original respondents and a selected sibling and from their spouses. Health, social, and economic data have been collected, with more recent initiatives including genetic studies of a sub-group of the cohort. The Health and Retirement Study based at the University of Michigan was initiated in 1992 and focused on the 51–61year age group. Subjects, now in their 70s and 80s, were interviewed every two years. Additional groups were added later including a cohort older than 70, a cohort of subjects who had birth dates in the years of the depression who were in their 60s at the time of recruitment, and the “war babies” cohort who were in their early 50s. Currently the study has captured data from ~20,000 persons. Over the years the investigation has expanded to include on site physical assessments, biomarkers and genetics, allowing the biological underpinnings of age-related disease and disorders to be uncovered (Duchowny et al., 2017; Mezuk et al., 2016). Frameworks such as the studies described above have great potential to uncover factors contributing to multi-morbidity, a key aspect in geriatric care and a major factor in loss of independence (Fabbri et al., 2015). As more molecular level data emerge from analysis of collected biospecimens from each of these and other longitudinal aging studies we can anticipate the emergence of a whole new perspective on aging biology in humans at unprecedented resolution.