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Could We Live Forever? The Latest Theories in Aging Research

Written by Kristine Yang '25

Edited by Wonjin Ko '26


Immortality may no longer be a power saved only for superheroes and vampires. Though aging has long been an inevitable process leading to death, recent research has shown glimpses of an alternate future – one in which we may have more control over our age, our health, and our lifespan.

Multiple theories on the science of aging and the possibilities of anti-aging have been published, however two independent views have received particular traction in this evolving field of research.

The Information Theory of Aging suggests that the loss of genetic information over time is the main cause of aging [1]. By this logic, organisms are born with a complete set of genetic information, and it is the degradation of this genetic code that leads to decreased functionality and failure of many cellular mechanisms which are often at the root of many age-related diseases [2].

Furthering this theory, researchers have identified epigenetic changes – modifications in gene expression that do not change the DNA sequence itself – as a possible contributing factor in aging, alongside DNA changes. Acting like an ‘on-off’ switch through mechanisms like DNA methylation, epigenetic changes can regulate which genes are active in a cell at any point in time [2].

To test whether older organisms retain the information needed to restore youthful epigenetic patterns, Harvard Medical School researcher David Sinclair reprogrammed the expression of the Oct4, Sox2, and Klf4 (OSK) genes in the eyes of mice. His lab showed that the reprogramming of OSK expression not only restored youthful DNA methylation patterns, but it also restored vision loss in a mouse model of aged mice [3].

Results from this study suggest that mammalian tissues retain youthful epigenetic data that can later be accessed to promote regeneration and improve function [3]. How the youthful epigenetic data is encoded and stored is a central question within the Information Theory of Aging, and genetic events such as covalent DNA modifications, DNA-binding proteins, RNA-guided chromatin modifying factors, and early-established RNA-DNA hybrids have all been proposed as possibilities [3]. Thus, by this theory, methods like gene therapy that can reprogram the epigenome have the possibility of repairing tissue and reversing age-related deterioration in humans [3].

As opposed to the Information Theory which states the loss of necessary genetic information causes aging, the Free Radical Theory alternatively posits that it is the overaccumulation of unnecessary molecules in the body that causes aging. Free radicals are unstable and highly reactive molecules that are naturally produced during normal cell metabolism [4]. The accumulation of these molecules in the body over time can damage proteins, DNA, and lipids which can cause age-related diseases such as heart conditions, cancer, and neurodegenerative disorders [5].

Because free radicals are a product of metabolism, slowing metabolism to decrease the rate of free radical production and subsequent molecular damage through caloric restriction has been shown to extend mammalian lifespans. Importantly, caloric restriction involves reducing caloric intake without the deprivation of essential nutrients. While studies have shown the effectiveness of caloric restriction in extending the lifespan in rodents, only recently have studies begun to test its effectiveness in human trials.

The most prominent human study was the CALERIE trial, a two-year study in which healthy adults were divided into a calorie reduction group and a control group [6]. Those in the caloric restriction group reduced their intake by 25%, and by the end of the study, experienced significant health benefits including lower cholesterol and blood pressure, in addition to improved insulin sensitivity index [5]. Given the brevity of the trial, the exact effect caloric restriction has on human longevity is unclear and additional follow-up with trial participants is underway to determine the effects on age-related disease prevention [6].

Both the Information Theory of Aging and the Free Radical Theory are prominent hypotheses in the evolving field of biomedical aging research. These two theories and others attempt to identify not only the biomarkers of aging, but also possible drivers of the aging process and age-related diseases on a cellular and molecular scale. Though the field of aging research is relatively nascent, studies have shown promises of a future in which our lifespan long-term health may not be dictated by our age.

 

References

[1] Karnaukhov AV, Karnaukhova EV, Sergievich LA, Karnaukhova NA, Bogdanenko EV, Manokhina IA, et al. Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation. Journal of Biophysics. 2015;2015:1–14.

[2] Dutchen S. Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It [Internet]. hms.harvard.edu. 2023. Available from: https://hms.harvard.edu/news/loss-epigenetic-information-can-drive-aging-restoration-can-reverse

[3] Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature [Internet]. 2020 Dec 1;588(7836):124–9. Available from: https://www.nature.com/articles/s41586-020-2975-4

[4] NCI Dictionary of Cancer Terms [Internet]. National Cancer Institute. Cancer.gov; 2019. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/free-radical

[5] Grabski I. Can Calorie Restriction Extend Your Lifespan? [Internet]. Science in the News. 2020. Available from: https://sitn.hms.harvard.edu/flash/2020/can-calorie-restriction-extend-your-lifespan/#:~:text=Moreover%2C%20since%20calorie%20restriction%20generally

[6] Waziry R, Ryan CP, Corcoran DL, Huffman KM, Kobor MS, Kothari M, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging [Internet]. 2023 Feb 9 [cited 2023 Mar 13];1–10. Available from: https://www.nature.com/articles/s43587-022-00357-y



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