Abstract
For most of their lifespan, the probability of death for many animal species increases with age. Gompertz law states that this increase is exponential. In this work, we have compared previously published data on the survival kinetics of different lines of progeric mice. Visual analysis showed that in six lines of these rapidly aging mutants, the probability of death did not strictly depend on age. In contrast, ten lines of progeric mice have survival curves similar to those of the control animals, that is, in agreement with Gompertz law, similar to the shape of an exponential curve upside down. Interestingly, these ten mutations cause completely different cell malfunctions. We speculate that what these mutations have in common is a reduction in the lifespan of cells and/or an acceleration of the transition to the state of cell senescence. Thus, our analysis, similar to the conclusions of many previously published works, indicates that the aging of an organism is a consequence of the aging of individual cells.
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References
Liao, C.-Y. and Kennedy, B. K. (2014) Mouse models and aging: longevity and progeria, Curr. Top. Dev. Biol., 109, 249-285, https://doi.org/10.1016/B978-0-12-397920-9.00003-2.
Gavrilov, L. A. and Gavrilova, N. S. (2015) New developments in the biodemography of aging and longevity, Gerontology, 61, 364-371, https://doi.org/10.1159/000369011.
Cabral, W. A., Tavarez, U. L., Beeram, I., Yeritsyan, D., Boku, Y. D., Eckhaus, M. A., Nazarian, A., Erdos, M. R., and Collins, F. S. (2021) Genetic reduction of mTOR extends lifespan in a mouse model of Hutchinson-Gilford Progeria syndrome, Aging Cell, 20, e13457, https://doi.org/10.1111/acel.13457.
Vermeij, W. P., Dollé, M. E. T., Reiling, E., Jaarsma, D., Payan-Gomez, C., Bombardieri, C. R., Wu, H., Roks, A. J. M., Botter, S. M., van der Eerden, B. C., Youssef, S. A., Kuiper, R. V., Nagarajah, B., van Oostrom, C. T., Brandt, R. M. C., Barnhoorn, S., Imholz, S., Pennings, J. L. A., de Bruin, A., Gyenis, Á., Pothof, J., Vijg, J., van Steeg, H., and Hoeijmakers, J. H. J. (2016) Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice, Nature, 537, 427-431, https://doi.org/10.1038/nature19329.
Wijshake, T., Malureanu, L. A., Baker, D. J., Jeganathan, K. B., van de Sluis, B., and van Deursen, J. M. (2012) Reduced life- and healthspan in mice carrying a mono-allelic BubR1 MVA mutation, PLoS Genet., 8, e1003138, https://doi.org/10.1371/journal.pgen.1003138.
Oh, Y. S., Kim, D. G., Kim, G., Choi, E.-C., Kennedy, B. K., Suh, Y., Park, B. J., and Kim, S. (2010) Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice, Aging Cell, 9, 810-822, https://doi.org/10.1111/j.1474-9726.2010.00614.x.
Goldman, R. D., Shumaker, D. K., Erdos, M. R., Eriksson, M., Goldman, A. E., Gordon, L. B., Gruenbaum, Y., Khuon, S., Mendez, M., Varga, R., and Collins, F. S. (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome, Proc. Natl. Acad. Sci. USA, 101, 8963-8968, https://doi.org/10.1073/pnas.0402943101.
Prasher, J. M., Lalai, A. S., Heijmans-Antonissen, C., Ploemacher, R. E., Hoeijmakers, J. H. J., Touw, I. P., and Niedernhofer, L. J. (2005) Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1–/– mice, EMBO J., 24, 861-871, https://doi.org/10.1038/sj.emboj.7600542.
Khokhlov, A. N., and Morgunova, G. V. (2017) Testing of geroprotectors in experiments on cell cultures: pros and cons, in Anti-Aging Drugs: From Basic Research to Clinical Practice (Vaiserman, A. M., ed) Royal Society of Chemistry, p. 53-74, https://doi.org/10.1039/9781782626602-00051.
Shabalina, I. G., Vyssokikh, M. Y., Gibanova, N., Csikasz, R. I., Edgar, D., Hallden-Waldemarson, A., Rozhdestvenskaya, Z., Bakeeva, L. E., Vays, V. B., Pustovidko, A. V., Skulachev, M. V., Cannon, B., Skulachev, V. P., and Nedergaard, J. (2017) Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1, Aging (Albany NY), 9, 315-339, https://doi.org/10.18632/aging.101174.
Choudhury, A. R., Ju, Z., Djojosubroto, M. W., Schienke, A., Lechel, A., Schaetzlein, S., Jiang, H., Stepczynska, A., Wang, C., Buer, J., Lee, H.-W., von Zglinicki, T., Ganser, A., Schirmacher, P., Nakauchi, H., and Rudolph, K. L. (2007) Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation, Nat. Genet., 39, 99-105, https://doi.org/10.1038/ng1937.
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This work was supported by the Russian Science Foundation (grant no. 22-24-00533).
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Sokolov, S.S., Severin, F.F. Two Types of Survival Curves of Different Lines of Progeric Mice. Biochemistry Moscow 89, 367–370 (2024). https://doi.org/10.1134/S0006297924020147
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DOI: https://doi.org/10.1134/S0006297924020147