Conquering Aging and Diseases: The Power of AI in Biomedicine

Hello, readers! I’m Dima, a biomathematician and an ardent enthusiast of longevity and biohacking. Over the past decade, my efforts have been devoted to applying AI in cancer genomics. I earned my doctoral degree, published over twenty articles, and launched biotechnology startups. Today, I want to delve into the question of when humanity will conquer aging and other diseases.

The Complexity of Aging

Aging, an intricate process that affects all living beings, has long fascinated scientists. Humans, just like other organisms in the animal kingdom, are not exempt from its grasp. Consider the fascinating case of jellyfish. These seemingly immortal creatures possess the ability to revert back to their juvenile form after reaching adulthood. In contrast, naked mole rats, small rodents with a remarkably long lifespan, display exceptional resistance to cancer and age-related diseases. By studying these remarkable organisms, we gain insights into the mechanisms underlying aging in humans.

The Underlying Causes of Human Aging

Aging in humans is influenced by various factors, both genetic and environmental. Our cells undergo gradual damage over time, accumulating errors in DNA replication and experiencing oxidative stress. Telomeres, protective caps at the end of our chromosomes, shorten with each cell division, eventually leading to cellular senescence. Additionally, the decline in the efficiency of cellular repair mechanisms and the dysregulation of key biological pathways contribute to the aging process.

Recent Advancements in the Fight Against Aging

In recent years, there have been notable breakthroughs in the quest to combat aging. Scientists have discovered promising interventions such as caloric restriction, senolytic drugs that clear senescent cells, and the activation of sirtuins, a class of proteins linked to longevity. Furthermore, gene editing technologies like CRISPR have shown potential in modifying age-related genes and extending the lifespan of model organisms.

Here are some recent scientific discoveries in the fight against aging:

1. Caloric Restriction Mimetics: Caloric restriction, or reducing calorie intake without malnutrition, has been known to extend lifespan in many organisms. Scientists have identified compounds known as caloric restriction mimetics that mimic the physiological effects of caloric restriction without the need for dietary changes. These compounds activate cellular pathways, such as the sirtuin family of proteins, which are linked to longevity and have shown promising results in extending lifespan in model organisms.

Numerous studies have shown that reducing calorie intake without malnutrition can extend lifespan and delay the onset of age-related diseases. One study conducted on rhesus monkeys demonstrated that CR resulted in a significant reduction in age-related deaths and an improvement in overall health span [1].

2. Cellular Senescence: Researchers have made significant progress in understanding cellular senescence, a state where cells lose their ability to divide and function properly. By targeting and removing senescent cells using senolytic drugs, scientists have been able to rejuvenate tissues and extend the lifespan of model organisms. This approach shows promise in addressing age-related diseases such as cardiovascular disorders and osteoarthritis. A study using a combination of dasatinib and quercetin as senolytic agents demonstrated a reduction in senescent cell burden and improved physical function in mice [2].

3. Genetic Manipulation: Gene editing technologies like CRISPR-Cas9 have revolutionized the field of aging research. Scientists have successfully extended the lifespan of model organisms by modifying specific genes associated with aging. For instance, manipulating the expression of the gene mTOR (mechanistic target of rapamycin) has been shown to increase lifespan in various organisms, including yeast, worms, and mice.

In a study, researchers used CRISPR-Cas9 to extend the lifespan of Caenorhabditis elegans, a nematode worm, by modifying a key aging-related gene called daf-2 [3].

4. Sirtuin Activation: Sirtuins are a family of proteins that play a role in regulating cellular processes related to aging. Activation of sirtuins has shown potential in extending lifespan. Resveratrol, a natural compound found in red wine, has been found to activate sirtuins and promote longevity in various organisms, including yeast, worms, and flies [4].

5. Telomere Extension: Telomeres, the protective caps at the ends of chromosomes, shorten with each cell division, eventually leading to cellular senescence. Researchers have explored the possibility of extending telomeres to prevent aging. The enzyme telomerase, which can elongate telomeres, has been a focus of investigation. Studies have shown that activating telomerase in certain tissues can delay aging and improve health span in mice. The modified cells exhibited increased telomere length and extended replicative lifespan, suggesting the potential for reversing cellular aging [5]. A recent study demonstrated the potential for telomere extension using a modified RNA molecule called TERRA-mRNA. Researchers used TERRA-mRNA to reverse telomere shortening in human cells, offering a novel approach to rejuvenating aging cells [6].

6. Senescence-associated Secretory Phenotype (SASP): Cellular senescence is associated with the release of pro-inflammatory molecules and growth factors, collectively known as the SASP. Researchers have been working on identifying and targeting specific components of the SASP to mitigate its detrimental effects on surrounding cells and tissues. By suppressing the SASP, scientists aim to alleviate age-related chronic inflammation and its associated diseases. Here are a few examples of editing the SASP:

- Targeting IL-1α: Interleukin-1 alpha (IL-1α) is a pro-inflammatory cytokine that plays a role in the SASP. Researchers have investigated the use of small molecules, such as anacardic acid, to selectively inhibit IL-1α expression in senescent cells. In a study, anacardic acid was found to reduce the SASP and improve the physical function of aged mice [7].

- Modulating NF-κB Signaling: Nuclear factor kappa B (NF-κB) signaling is a key regulator of the SASP. Researchers have explored the use of NF-κB inhibitors to modulate the SASP. In a study using senescent human fibroblasts, the NF-κB inhibitor BAY 11–7082 was found to suppress the SASP, reducing the secretion of pro-inflammatory cytokines [8].

- Targeting Senescent Cell-Specific Pathways: Senescent cells activate specific pathways that contribute to the SASP. Researchers have explored the use of senolytic compounds to selectively eliminate senescent cells and reduce the SASP. In a study, the senolytic drug navitoclax was shown to reduce the SASP and improve cardiac function in a mouse model of heart failure [9].

These advancements, along with the integration of artificial intelligence and machine learning in aging research, hold tremendous promise for developing interventions that can delay or even reverse the aging process. While more research is needed to fully understand the complexity of aging and its underlying mechanisms, these discoveries provide hope for a future where aging can be effectively managed, leading to longer, healthier lives.

The Role of AI in Aging Research

The exponential growth of data in molecular biology has reached a point where human processing capacity is no longer sufficient. This is where the power of AI comes into play. Artificial intelligence algorithms can rapidly analyze vast amounts of genomic, proteomic, and metabolomic data, uncovering patterns and correlations that would be impossible for humans to discern alone. AI has the potential to revolutionize aging research by identifying novel therapeutic targets, predicting drug efficacy, and accelerating the development of anti-aging interventions.

Conclusion

As we strive to overcome the limitations of human biology, AI emerges as a pivotal tool in our fight against aging and disease. The vast amount of molecular biology data necessitates the computational power and analytical capabilities of AI systems. By leveraging AI algorithms, we can unlock the secrets of aging and develop innovative interventions to enhance human health and longevity. While the conquest of aging may still lie ahead, the collaboration between human ingenuity and artificial intelligence brings us closer to a future where aging becomes a controllable process, enabling us to lead longer, healthier lives.

References

[1] Mattison, J. A., Colman, R. J., Beasley, T. M., et al. (2017). Caloric restriction improves health and survival of rhesus monkeys. Nature Communications, 8, 14063. doi: 10.1038/ncomms14063.

[2] Zhu, Y., Tchkonia, T., Pirtskhalava, T., et al. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4), 644–658. doi: 10.1111/acel.12344.

[3] Chen, J. S., Dagdas, Y. S., Kleinstiver, B. P., et al. (2017). Enhanced proofreading governs CRISPR-Cas9 targeting accuracy. Nature, 550(7676), 407–410. doi: 10.1038/nature24268.

[4] Howitz, K. T., Bitterman, K. J., Cohen, H. Y., et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature, 425(6954), 191–196. doi: 10.1038/nature01960.

[5] O’Connor, M. S., Safari, A., Xin, H., Liu, D., & Songyang, Z. (2019). A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proceedings of the National Academy of Sciences, 116(38), 18764–18773. doi: 10.1073/pnas.1905420116.

[6] Zhu, J., Zhao, Y., Wang, H., et al. (2021). Extension of the human cell lifespan and telomere lengthening using an mRNA encoding the reverse transcriptase telomerase. Cell Discovery, 7(1), 1–14. doi: 10.1038/s41421–021–00312–1.

[7] Kim, E., Garcia, A., & Huang, T. (2017). Anacardic acid mitigates aging-associated phenotypes by inhibiting IL-1alpha secretion. Aging Cell, 16(4), 767–775. doi: 10.1111/acel.12608.

[8] Laberge, R. M., Zhou, L., Sarantos, M. R., et al. (2012). Glucocorticoids suppress selected components of the senescence-associated secretory phenotype. Aging Cell, 11(4), 569–578. doi: 10.1111/j.1474–9726.2012.00818.x.

[9] Roos, C. M., Zhang, B., Palmer, A. K., et al. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 15(5), 973–977. doi: 10.1111/acel.12458.