A Frailty Index Quantifies Mortality Risk in Humans and in Mice

Developers

K. Rockwood, J. M. Blodgett, A. Mitnitski, E. Gregson, S. E. Howlett, etc.

Description of the technology

Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index.

The technology allows extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 [1.04–1.05] in humans; 1.15 [1.12–1.18] in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.

However, this technology has still some shortcomings. The designs of the two data sources are different. The mouse data represent a small cohort followed to extinction, whereas the study of human ageing includes the cross-sectional data on the human populations with a much larger sample size and with necessarily time-limited mortality follow-up. The authors attempted to mitigate the small mouse sample size by multiple observations. Translation in the present study was done from human studies that then were employed in mice. «Back translation» is now under way. The version of the mouse frailty index used was modelled on a comprehensive geriatric assessment, and it is suitable for longitudinal use. In contrast, the initial mouse frailty index chiefly used laboratory test data, arising in the context of terminal experiments. More recently, the authors of the technology have developed a version of the frailty index for use in humans that employs only laboratory test data, as a means of understanding subclinical aspects of frailty. The term «frailty index» serves now for discovery of targets for treatment and as integrative method for measurement of ageing processes. For these reasons, the combining of its clinical and laboratory-based versions, in both humans and in mice, is a challenge for future investigations of this group of developers.

Practical application

The technology is important, because it raises a very serious question about interpretation of research results, carried out in animal models and translation of these results to the studies of human ageing. The technology proposes a promising way to solve this challenge.

Laboratories

• Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax (Canada)
• Department of Pharmacology, Dalhousie University, Halifax (Canada)
• Department of Physiology & Biophysics, Dalhousie University, Halifax (Canada)

Links

Publications

• Rockwood, K. et al. «A Frailty Index Based On Deficit Accumulation Quantifies Mortality Risk in Humans and in Mice." 7 Scientific Reports (2017): 43068.
• Mitnitski, A. & Rockwood, K. «The rate of aging: the rate of deficit accumulation does not change over the adult life span." 17 Biogerontology (2016): 199–204.
• Armstrong, J.J. et al. «Frailty in the Honolulu-Asia Aging Study: deficit accumulation in a male cohort followed to 90% mortality." 70 J Gerontol A Biol Sci Med Sci. (2015): 125–131.