Aging has been a topic of both scientific and philosophical debate throughout history. In her book “Coming of Age”, the existentialist philosopher Simone de Beauvoir writes, “I am incapable of conceiving infinity, and yet I do not accept finity. I want this adventure that is the context of my life to go on without end.”[1] The tension between the finite nature of the human lifespan and the search for eternality is similarly reflected in aging research developments and the search for mechanisms of “reverse aging”.
Part of what makes aging fascinating is our lack of understanding of its causes. It is a universal, intrinsic process, yet is also forcibly influenced by exogenous conditions [2]. It is often associated with the passage of time, yet there is a difference between chronological age– how long a person has existed– and apparent biological age– how old a person’s cells actually appear to be [3]. This discrepancy has driven research into the biological mechanisms behind gaps in these two measures of age. Most of the many theories of aging that have emerged fall into two categories: program and damage theories [4]. Program theories are driven by natural selection, suggesting that a limited lifespan is deliberately programmed because of the evolutionary benefits that a shorter lifespan brings [4]. Damage theories emphasize the absence of natural selection acting post-reproduction, instead emphasizing the role of accumulated damage on a biochemical level [4]. While there is growing evidence for various versions of program and damage theory, the exact contributions of these different factors remain unknown.
As we increase our understanding of the drivers of biological aging, interest has developed in going a step further to reverse the aging process. While efforts to slow the aging process have been in progress for some time, recent groundbreaking studies have suggested the possibility of running aging in reverse. Two of the most promising age-reversal studies to date have taken different approaches, one aiming to chemically reprogram aged cells and the other focusing on eliminating them altogether. The former, published in 2023 by Yang et al., demonstrated that several chemical mixtures were able to restore epigenetic marks characteristic of youthful cells in a timeframe of less than a week [5]. In contrast, the latter, published earlier this year by Amor et al., demonstrated the ability of CAR T cells to target and destroy uPAR-positive senescent cells, a subset of cells that accumulates with age in humans [6]. While these recent scientific breakthroughs point to the possibility of targeting and reversing the mechanisms of aging in the lab, this work is still at an early stage and has not been received without criticism. In addition to a host of ethical considerations, there are also doubts about the ability to translate this research from the context of cells to humans. Jesse Kurland, an aging researcher at the University of Colorado Boulder, points to the complications associated with such research, stating that he finds it “hard to imagine how a process that disrupts our tissues universally in such complex ways, and in fundamental cellular processes like transcription (the process in which information in a strand of DNA is copied into a new molecule of messenger RNA), could be fixed by altering one, or even handfuls, of genes” [7].
While our ability to reverse aging outside of the laboratory is not yet a reality, the scientific foundations have been laid, meaning that we are now able to envision the “imperceptible infinity” presented by de Beauvoir like never before. But as progress is made on scientific questions around aging, ethical questions arise around the implementation of reverse aging therapies. A series of logistical questions arise, such as the prospect of exacerbating the existing problem of overpopulation, as well as concerns around access across various income and country lines [8]. There is also a series of larger moral and philosophical questions around extending lifespan, such as the theory that the existence of a finite end provides meaning and motivation, and that changing our relationship to death could fundamentally alter the human experience. While the possibility of reversing aging is exciting and commands attention from a scientific perspective, an equally rigorous consideration must be given regarding the ethics of translating these breakthroughs into the clinic.
Designed By: Makayla Gorski
Edited By: Angie Huang
References
[1] De Beauvoir, Simone. The Coming of Age. New York, Putnam, 1972.
[2] Borrás C (2021) The Challenge of Unlocking the Biological Secrets of Aging. Front. Aging 2:676573. doi: 10.3389/fragi.2021.676573.
[3] “What Is Your Actual Age?” Northwestern Medicine, www.nm.org/healthbeat/medical-advances/science-and-research/What-is-Your-Actual-Age.
[4] Da Costa, João Pinto et al. “A synopsis on aging-Theories, mechanisms and future prospects.” Aging research reviews vol. 29 (2016): 90-112. doi:10.1016/j.arr.2016.06.005.
[5] Yang J, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, Tian X, Ibrahim N, Chen Z, Griffin PT, Arnold M, Li J, Martinez OA, et al. Chemically induced reprogramming to reverse cellular aging. Aging (Albany NY). 2023 Jul 12; 15:5966-5989 . https://doi.org/10.18632/aging.204896.
[6] Amor, C., Fernández-Maestre, I., Chowdhury, S. et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nature Aging (2024). https://doi.org/10.1038/s43587-023-00560-5.
[7] Sauer, Rachel. “Bad News for Boomers: There’s No Magic Cure for Aging.” Colorado Arts and Sciences Magazine, University of Colorado Boulder, 27 July 2023, www.colorado.edu/asmagazine/2023/07/27/bad-news-boomers-theres-no-magic-cure-aging.
[8] Steele, Andew. “Science Says We Could ‘Cure’ Ageing. but Should We?” Polytechnique Insights, Institut Polytechnique de Paris, 20 Sept. 2022, www.polytechnique-insights.com/en/columns/health-and-biotech/science-says-we-could-cure-ageing-but-should-we/.
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