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What Are Zombie Cells: The Silent Saboteurs of Longevity

April 25, 2024

In the study of longevity, one term that frequently crops up is “senescent cells,” often referred to as “zombie cells.” These cells, once active participants in the body’s essential functions, are old, worn-out cells that don't die but instead secrete dangerous inflammatory molecules called cytokines and other signaling molecules that drive even more inflammation and accelerate aging. They are caused by DNA damage, critically short telomeres, and chemical or toxic stress including our inflammatory diet and lifestyle.

In fact, the accumulation of zombie cells is one of the hallmarks of aging and a key contributor to inflammation, metabolic dysfunction, and all age-related diseases, including cancer, heart disease, liver disease, dementia, Parkinson’s, cataracts, arthritis, and muscle loss or sarcopenia.

Fortunately, the accumulation of these cells isn’t inevitable, and there are simple strategies we can take to avoid it.

What Are Zombie Cells?

Zombie or senescent cells are cells that have stopped dividing but do not undergo programmed cell death. They are triggered by various factors, including DNA damage, telomere shortening, oxidative stress, and oncogenic stress as well as bad diet, toxins, and stress.

Because they don’t die, senescent cells accumulate with age and can spread throughout the body, releasing inflammatory factors that can damage surrounding tissues, disrupt normal cell function, contribute to the decline of organ function, and increase the risk of age-related diseases.

Strategies to Combat Zombie Cells

The fight against senescent cells is multifaceted, involving lifestyle changes, dietary interventions, and emerging pharmaceuticals known as senolytics and senomorphics. Here are practical strategies to combat these cellular saboteurs:

1. Embrace an Active Lifestyle

• Regular Exercise: Physical activity has been shown to reduce the accumulation of senescent cells by promoting their clearance and improving immune function.
• Stress Management: Chronic stress can accelerate the production of senescent cells. Techniques such as mindfulness, meditation, and yoga can help manage stress levels.

2. Optimize Your Diet

• Antioxidant-Rich Foods: Consuming foods high in antioxidants can reduce oxidative stress, one of the triggers of cellular senescence. Include colorful fruits and vegetables including berries, nuts, green leafy vegetables, and dark chocolate in your diet.
• Caloric Restriction and Intermittent Fasting: These dietary approaches have been shown to reduce the burden of senescent cells by enhancing autophagy, the body's way of cleaning out damaged cells. Try not eating for at least 12 hours, ideally 14 hours, overnight between dinner and breakfast.

3. Consider Senolytic and Senomorphic Agents

• Senolytics: These are naturally occurring compounds like flavonoids that selectively induce death in senescent cells and can be either taken as supplements or found in many fruits and vegetables. These include fisetin from strawberries, persimmons, apples, cucumbers, and onions; luteolin, found in carrots, broccoli, artichoke, onion leaves, chrysanthemum flowers, cabbages, and apple skins; quercetin, found in apples, grapes, berries, broccoli, citrus fruits, and cherries; as well as curcumin, found in turmeric. In fact, one study combining quercetin with a leukemia chemotherapy drug called dasatinib was found to reverse biological aging in clinical trials in part by killing zombie cells, extending the lifespan in mice by 36%.
• Senomorphics: These agents do not kill senescent cells but instead suppress the harmful pro-inflammatory cytokines, chemokines, growth factors, and proteases that senescent cells secrete. They are being explored as a way to mitigate the negative effects of senescent cells, including age-related inflammation, tissue dysfunction, and even the progression of diseases such as cancer, without eliminating them. Compounds with senomorphic properties include quercetin, fisetin, resveratrol, curcumin, and piperlongumine, an alkaloid commonly derived from long pepper.ng pepper.

4. Monitor Your Health

• Regular Check-Ups: Early detection and management of chronic conditions can prevent or reduce the accumulation of senescent cells. Regular medical check-ups and screenings are essential. I recommend becoming a member of Function Health to evaluate your levels of inflammation and more through a panel of 100+ lab tests and biomarkers.

5. Consider Hyperbaric Oxygen Therapy

• HBOT and Senescent Cells: HBOT involves breathing 100% oxygen in a pressurized environment, typically around 2 atmospheres (ATM), which is equivalent to being 66 feet under the ocean. Unlike normal air, which contains 21% oxygen, this environment provides a hormetic stress that promotes healing and longevity. Initially used for scuba divers and athletes, and to treat serious medical conditions, research has shown that HBOT can reduce the number of senescent cells by up to 37%. It does this by inducing these cells to die off, thereby reducing inflammation and their harmful effects on nearby healthy cells.

Key Takeaways for Longevity

• Active Lifestyle: Engage in regular exercise and stress-reducing activities to combat the accumulation of senescent cells.
• Diet Matters: Incorporate a diet rich in antioxidants and consider caloric restriction or intermittent fasting to enhance your body's defense against aging.
• Health Monitoring: Regular health check-ups can help manage risk factors that contribute to the accumulation of senescent cells.

The science of senescent cells unveils a crucial aspect of aging and presents actionable strategies to mitigate their impact. By adopting a proactive approach toward lifestyle, diet, and emerging therapies, we can pave the way for healthier, longer lives, free from the grasp of zombie cells.

References

1. Ding YN, Wang HY, Chen HZ, Liu DP. Targeting senescent cells for vascular aging and related diseases. J Mol Cell Cardiol. 2022;162:43-52. doi:10.1016/j.yjmcc.2021.08.009

2. Mohamad Kamal NS, Safuan S, Shamsuddin S, Foroozandeh P. Aging of the cells: Insight into cellular senescence and detection Methods. Eur J Cell Biol. 2020;99(6):151108. doi:10.1016/j.ejcb.2020.151108

3. Kuehnemann C, Wiley CD. Senescent cells at the crossroads of aging, disease, and tissue homeostasis. Aging Cell. 2024;23(1):e13988. doi:10.1111/acel.13988

4. Childs BG, Gluscevic M, Baker DJ, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16(10):718-735. doi:10.1038/nrd.2017.116

5. >van Deursen JM. The role of senescent cells in ageing. Nature. 2014;509(7501):439-446. doi:10.1038/nature13193

6. Gasek NS, Kuchel GA, Kirkland JL, Xu M. Strategies for Targeting Senescent Cells in Human Disease. Nat Aging. 2021;1(10):870-879. doi:10.1038/s43587-021-00121-8

7. Csekes E, Račková L. Skin Aging, Cellular Senescence and Natural Polyphenols. Int J Mol Sci. 2021;22(23):12641. Published 2021 Nov 23. doi:10.3390/ijms222312641

8. Liu RM. Aging, Cellular Senescence, and Alzheimer's Disease. Int J Mol Sci. 2022;23(4):1989. Published 2022 Feb 11. doi:10.3390/ijms23041989

9. Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of Cellular Senescence. Trends Cell Biol. 2018;28(6):436-453. doi:10.1016/j.tcb.2018.02.001

10. Zhang L, Pitcher LE, Yousefzadeh MJ, Niedernhofer LJ, Robbins PD, Zhu Y. Cellular senescence: a key therapeutic target in aging and diseases. J Clin Invest. 2022;132(15):e158450. doi:10.1172/JCI158450

11. Herranz N, Gil J. Mechanisms and functions of cellular senescence. J Clin Invest. 2018;128(4):1238-1246. doi:10.1172/JCI95148

12. Hachmo Y, et. al., Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY). 2020 Nov 18;12(22):22445-22456

13. Hadanny A, Efrati S. The Hyperoxic-Hypoxic Paradox. Biomolecules. 2020 Jun 25;10(6):958.

14. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658