Cellular Senescence Why We Need to Pay Attention
NUTRITION
Cellular senescence is an intrinsic aging process where cells have permanently stopped dividing but do not die off as would be normal or expected.
Lynn Toohey
PhD
This is because as we age, the ability to clear these senescent cells is diminished. The senescent cells experience no more growth, but since they don’t die and can’t be cleared efficiently, they accumulate.
Problems arise because a) these cells still maintain high metabolic activity; b) the accumulation of these senescent cells causes an increase in factors that further the inhibition of normal cell cycles; and c) most importantly, the accumulation also causes a hypersecretory state and release of harmful chemicals collectively known as SASP (senescence-associated secretory phenotype). SASP includes pro-inflammatory cytokines, chemokines, growth factors, proteases, lipids, and extracellular matrix components.
Normally, the immune system would efficiently clear these cells from the system. However, the immune system’s ability to perform declines as we age and we are left with this accumulation of SASP-producing cells that:
• Promote chronic, low-grade inflammation.
• Damage neighboring cells that lead to tissue dysfunction.
• Accelerate aging and increase the likelihood of health issues. SASP has been an overlooked pathway of cellular destruction and inflammation that wreaks havoc on neighboring cells and majorly influences the surrounding tissue microenvironment, ultimately affecting and changing systemic biological functions.1
SASP as a Biomarker for Age-Related Health: In viewing SASP as a potential driver of age-related dysfunction, scientists tested whether circulating concentrations of SASP proteins reflect age and propensity for health issues in humans. A community-based sample of people was studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes.
Seven SASP factors (composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL15) predicted adverse events markedly better than a single SASP protein or age.
Altogether, it was concluded that SASP proteins were positively associated with age, frailty, and adverse post-surgery outcomes, and that, “Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.”2
Epigenetic Reprogramming: Senescent cell nuclei undergo epigenetic reprogramming, which regulates SASP expression. Our epigenetic input, such as diet, lifestyle, and nutritional supplementation, influences this epigenetic reprogramming to a great extent. It is generally agreed that discovery of SASP has shifted the paradigm of senescence research beyond its conventional focus on permanent proliferation arrest and has allowed us to note how SASP can elucidate many aspects of senescence.
Deciphering its role and regulation holds tremendous potential for understanding aging and age-associated physiology.3 Lifestyle practices that can be incorporated to reduce SASP cell destruction and improve clear ance of senescent cells include:
• Regular Exercise: Physical activity has been shown to reduce inflammation and promote a healthier cellular environment.
• Anti-Inflammatory Diet: Focus on a diet with organic foods rich in antioxidants, flavonoids, polyphenols, healthy fats, and cruciferous vegetables. Adding sprouts will supply sulforaphane that can efficiently clear senescent cells. Epigallocatechin gallate (EGCG) is a compound abundant in green tea; it exhibits antioxidant properties and is believed to mitigate some of the harmful effects of senescent cells.4
• Fasting and Caloric Restriction: Intermittent fasting and caloric restriction have been linked to reduced markers of cellular aging.
• Manage Stress: Chronic stress can accelerate aging; practices like meditation and yoga may help mitigate its effects.
• Prioritize Sleep: Adequate, high-quality sleep supports cellular repair and regeneration.
Nutritional Supplementation Protocol: The good news is that several natural compounds have what is called senolytic (senescent cell-destroying) or senomorphic (senescent cellmodulating) properties.
With a focus on cellular senescence, emerging studies demonstrate that nutritional elements, such as carbohydrates, proteins, fatty acids, vitamins, minerals, polyphenols, probiotics, and other nutrients, can influence multiple aspects of cellular senescence.5
Specific nutrients that support SASP clearance:
• NAC (N-acetyl cysteine) — Studies suggest that NAC is an efficient SASP nutrient that inhibits cell senescence and all the associated secretions from SASP In fact, it is suggested that NAC can even help make up for estrogen deficiency-induced bone loss by inhibiting oxidative stress and DNA damage and by the mechanism of inhibiting SASP6
• Quercetin is a flavonoid found in foods such as apples, onions, and berries. It has strong antioxidant and anti-inflammatory properties. Studies suggest quercetin can selectively eliminate senescent cells and influence markers of aging.7
• Probiotics and prebiotics can be useful in mitigating cellular senescence and aging. In fact, it appears that the observed anti-cellular senescence effects of many dietary constituents, including phytomolecules such as quercetin, could be mediated through the modulation of the gut microbiota composition.8 It is believed that SASP secretions follow microbial imbalance, and the skin is an area where senescent cells tend to accumulate. Research confirms the role of preand probiotics in skin health in particular and cellular senescence in general9
• Curcumin is known for its powerful effects on the inflammatory process. It helps regulate the pathways associated with senescence and may reduce the negative impact of SASP factors.10
• Resveratrol: Found in red grapes and blueberries, resveratrol activates pathways that support healthy cellular aging. It may also enhance the body’s ability to clear dysfunctional cells.11
• Sulforaphane: Present in cruciferous vegetables like broccoli and Brussels sprouts, sulforaphane activates detoxification pathways that support the integrity of cells and reduce senescence markers.12 Sulforaphane is named by researchers as one of the Nrf2-interacting natural compounds with senolytic activity that can positively influence SASP. The Nrf2 pathway is recognized as a friendly pathway for cellular integrity. Some of the other nutrients mentioned along with sulforaphane by those researchers for senolytic activity included quercetin, curcumin, resveratrol, and the EGCG in green tea.13
• Apigenin is found in relatively high quantities in dried parsley — 4,500 mg/100 gm (the next highest food source is chamomile at 500 mg/100 gm). Apigenin is a powerful biochemical that has been identified as one of the nutrients with the ability to suppress SASP and resulting paracrine effects to proximal cells.14
Conclusion
While senescent cells can play a role in protecting the body during times of stress, their accumulation contributes to aging and health issues. Incorporating natural compounds such as quercetin, probiotics/prebiotics, curcumin, resveratrol, and sulforaphane, along with healthy lifestyle practices, can help the body manage senescent cells and promote overall well-being. Further research continues to uncover the potential of these strategies for enhancing health and longevity.
Dr. Lynn Toohey organizes seminars, acts as a nutritional consultant to Nutri-West (www.nutriwest.com), and authored the Functional Health Evaluation program that analyzes blood tests and DNA raw data (www.FHEcloud.com). Dr. Toohey can be reached at 866-271-8888 or by email at [email protected] with any questions.
References
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