Researchers are keeping a bank of induced pluripotent stem cells (iPSCs) derived from centenarians and their descendants. They describe the purpose of this bank and its uses in Aging Cell.
A category of their own
Centenarians don’t merely live for a hundred years; they spend more time in good health (healthspan) than other people. This is called the compression of morbidity [1]. This makes them ideal for research, as people attempt to assess why they are so resistant to various age-related disorders such as Alzheimer’s disease [2]. However, researchers have still not discovered the biological methods by which centenarians retain such longevity [3].
At least part of this longevity is genetic. The descendants of centenarians are less vulnerable to age-related diseases [4] and are younger according to epigenetic clocks [5]. Therefore, cells derived from centenarians, including iPSCs that can transform into any other type of cell, will retain these genetic advantages [6].
Old cells can grow like young cells
These researchers built their bank using peripheral blood mononuclear cells (PBMCs) and the iPSCs derived from them. A total of 45 centenarians were recruited for this study, with 45 descendants included as well. Over three-fourths of the centenarians had healthy brains at age 100, and more than four-fifths were able to live independently at that age.
While offspring data was less consistent, centenarians were confirmed to have slightly slower epigenetic aging than non-centenarians. In accordance with previous research, immune cells derived from centenarians were found to have named longevity-promoting genes [7].
Creating iPSCs from such old people was surprisingly easy; generating them and having them proliferate was no different than it was in cells derived from younger people. The researchers were able to program these cells into forebrain neurons. Regardless of the age of the subjects, all cells were equally likely to correctly differentiate into these cells. However, some cells in three male centenarians lacked their Y chromosomes; this “mosaic” loss is linked to age-related diseases [8].
The researchers tout their new biobank as a permanent resource that can aid future research, and propose that it might be used in finding effective therapies against age-related diseases. Additionally, it better enables the identification of people who are likely to live for a very long time, thus allowing them to be more easily included in future research. If these iPSCs can be used to create organoids that simulate human organs, it might be possible to validate therapies against age-related diseases that work even on the oldest old.
Literature
[1] Fries, J. F., Bruce, B., & Chakravarty, E. (2011). Compression of morbidity 1980–2011: a focused review of paradigms and progress. Journal of aging research, 2011(1), 261702.
[2] Andersen, S. L. (2020). Centenarians as models of resistance and resilience to Alzheimer’s disease and related dementias. Advances in geriatric medicine and research, 2(3).
[3] Lin, J. R., Sin-Chan, P., Napolioni, V., Torres, G. G., Mitra, J., Zhang, Q., … & Zhang, Z. D. (2021). Rare genetic coding variants associated with human longevity and protection against age-related diseases. Nature Aging, 1(9), 783-794.
[4] Newman, A. B., Glynn, N. W., Taylor, C. A., Sebastiani, P., Perls, T. T., Mayeux, R., … & Hadley, E. (2011). Health and function of participants in the Long Life Family Study: a comparison with other cohorts. Aging (Albany NY), 3(1), 63.
[5] Horvath, S., Pirazzini, C., Bacalini, M. G., Gentilini, D., Di Blasio, A. M., Delledonne, M., … & Franceschi, C. (2015). Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY), 7(12), 1159.
[6] Bucci, L., Ostan, R., Cevenini, E., Pini, E., Scurti, M., Vitale, G., … & Monti, D. (2016). Centenarians’ offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview. Aging (Albany NY), 8(3), 510.
[7] Karagiannis, T. T., Dowrey, T. W., Villacorta-Martin, C., Montano, M., Reed, E., Belkina, A. C., … & Sebastiani, P. (2023). Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity. EBioMedicine, 90.
[8] Thompson, D. J., Genovese, G., Halvardson, J., Ulirsch, J. C., Wright, D. J., Terao, C., … & Perry, J. R. (2019). Genetic predisposition to mosaic Y chromosome loss in blood. Nature, 575(7784), 652-657.
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