Research Paper Volume 11, Issue 7 pp 2098—2110
In mice transgenic for IGF1 under keratin-14 promoter, lifespan is decreased and the rates of aging and thymus involution are accelerated
- 1 Department of Carcinogenesis and Oncogerontology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg 197758, Russia
- 2 Laboratory of Experimental Models, State Institute of Genetic and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kiev 04114, Ukraine
received: December 12, 2018 ; accepted: March 31, 2019 ; published: April 13, 2019 ;https://doi.org/10.18632/aging.101903
How to Cite
Copyright: Anisimov et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
IGF1 signaling is supposedly a key lifespan determinant in metazoans. However, controversial lifespan data were obtained with different means used to modify IGF1 or its receptor (IGF1R) expression in mice. The emerging puzzle lacks pieces of evidence needed to construct a coherent picture. We add to the available evidence by using the Gompertz model (GM), with account for the artifactual component of the Strehler-Mildvan correlation between its parameters, to compare the survival patterns of female FVB/N and FVB/N-derived K14/mIGF1 mice. In K14/mIGF1 vs. FVB/N mice, the rate of aging (γ) is markedly increased without concomitant changes in the initial mortality (μ0). In published cases where IGF1 signaling was altered by modifying liver or muscle IGF1 or whole body IGF1R expression, lifespan changes are attributable to μ0. The accelerated aging and associated tumor yield in K14/mIGF1 mice are consistent with the finding that the age-associated decreases in thymus weight and serum thymulin are accelerated in K14/mIGF1 mice. Our results underscore the importance of accounting for the mathematical artifacts of data fitting to GM in attempts to resolve discrepancies in survival data and to differentiate the contributions of the initial mortality and the rate of aging to changes in lifespan.