Anti-Aging and Longevity Science in Africa: Senolytics and the Future of Cellular Rejuvenation

Abstract

Senescence—the process by which cells stop dividing and accumulate over time—plays a pivotal role in aging and age-related diseases. Senolytics, a promising new class of drugs, selectively eliminate these dysfunctional cells, potentially delaying aging and improving healthspan. This paper explores the science behind senolytics, recent breakthroughs in clinical trials, and the implications for African populations facing a surge in age-related diseases. It calls for inclusive longevity science research tailored to African contexts, highlighting both opportunities and challenges for implementation.

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Introduction

Aging populations are increasingly becoming a global reality, including in sub-Saharan Africa where life expectancy has risen significantly due to improvements in healthcare, nutrition, and disease management. With this demographic shift, age-associated diseases such as type 2 diabetes, cardiovascular diseases, neurodegeneration, and frailty syndromes are on the rise (World Health Organization [WHO], 2023). Longevity science—particularly interventions targeting the biological processes of aging—offers a transformative approach to managing these health challenges. Among these interventions, senolytics have emerged as a promising class of therapeutic agents that specifically target and eliminate senescent cells. This paper provides an overview of senolytics, their mechanisms of action, clinical evidence, and potential applicability in African healthcare systems.

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Cellular Senescence and Pathophysiology of Aging

Cellular senescence refers to the permanent cessation of cell division, typically in response to DNA damage, oxidative stress, oncogene activation, or telomere shortening. Senescent cells adopt a senescence-associated secretory phenotype (SASP), releasing pro-inflammatory cytokines, chemokines, proteases, and growth factors (Childs et al., 2015). While initially protective—preventing the proliferation of damaged cells—chronic accumulation of senescent cells leads to tissue dysfunction, chronic inflammation, and progression of diseases such as atherosclerosis, osteoarthritis, and Alzheimer’s disease (Campisi et al., 2019).

In African populations where communicable and non-communicable disease burdens intersect, the accumulation of senescent cells could compound health vulnerabilities. Environmental stressors such as chronic infections (e.g., HIV) and nutritional deficiencies may accelerate senescence and inflammation-related pathologies (Onyango et al., 2020).

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Senolytics: Mechanisms and Leading Compounds

Senolytics are pharmacological agents that selectively induce apoptosis in senescent cells without affecting proliferating or quiescent cells. They act by inhibiting pro-survival pathways that are upregulated in senescent cells—commonly BCL-2 family proteins, PI3K/AKT, and p53 pathways (Zhu et al., 2015).

Key Senolytic Agents:

• Dasatinib: A tyrosine kinase inhibitor used in leukemia, shown to selectively clear senescent preadipocytes.
• Quercetin: A flavonoid found in fruits and vegetables that induces apoptosis in senescent endothelial and bone marrow-derived cells.
• Fisetin: A natural compound with anti-inflammatory and senolytic properties.
• Navitoclax (ABT-263): Targets BCL-2/BCL-xL proteins, potent in clearing senescent hematopoietic cells.

Combination therapies, such as Dasatinib + Quercetin (D+Q), have demonstrated synergistic effects in reducing senescent cell burden and improving tissue homeostasis in mouse models (Xu et al., 2018).

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Clinical Trials and Research Breakthroughs

Significant progress has been made in translating senolytics into human clinical trials. Below are major recent findings:

1. Senolytics in Idiopathic Pulmonary Fibrosis (IPF):

The first-in-human pilot study using D+Q for IPF patients showed improved physical function and reduced senescent cell markers in peripheral blood (Justice et al., 2019).
DOI: 10.1016/j.ebiom.2019.04.022

2. Fisetin in Older Adults (AFFIRM-LITE Trial):

A randomized, placebo-controlled trial is underway to evaluate fisetin in reducing inflammation and improving physical function in older adults.
ClinicalTrials.gov ID: NCT03675724

3. Senolytics in COVID-19 Recovery:

Because senescent cells are implicated in heightened inflammatory responses, senolytics have been studied for COVID-19 complications, particularly in older adults. The SENOX trial investigates D+Q to reduce post-COVID inflammation.
ClinicalTrials.gov ID: NCT04537299

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Relevance to African Healthcare Systems

Africa faces unique challenges and opportunities when considering the implementation of senolytic therapies:

Challenges:

• Cost and Access: Many senolytics are derived from expensive or patented compounds.
• Diagnostic Infrastructure: Lack of access to biomarkers for senescence impairs targeted therapy.
• Regulatory Gaps: African regulatory bodies have limited frameworks for anti-aging interventions.

Opportunities:

• Natural Compound Potential: Africa’s biodiversity offers potential for indigenous senolytic compounds. For instance, polyphenols in Moringa oleifera and rooibos have antioxidant and anti-inflammatory properties (Ogunlesi et al., 2020).
• Integrative Approaches: Traditional medicine could be leveraged alongside senolytics, especially in areas with strong cultural resonance.
• Population-Based Healthspan Gains: Targeting biological aging could mitigate multiple NCDs simultaneously—aligning with universal healthcare goals.

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Ethical and Social Considerations

The application of senolytics raises ethical concerns around equitable access, anti-aging elitism, and potential misuse. For Africa, ensuring that longevity science does not widen health inequities is critical. Local bioethics frameworks must be developed to govern these emerging technologies in culturally and socially appropriate ways (Tangwa, 2017).

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Conclusion

Senolytics represent a groundbreaking frontier in anti-aging and longevity science. By targeting cellular senescence, these drugs have the potential to transform how we treat age-related diseases and extend healthspan—especially in resource-limited settings. For African countries, strategic investments in longevity research, traditional pharmacognosy, and health system readiness are essential to harness this revolution in a socially just and effective manner.

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References

Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. Nature, 571(7764), 183–192. https://doi.org/10.1038/s41586-019-1365-2

Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015). Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nature Medicine, 21(12), 1424–1435. https://doi.org/10.1038/nm.4000

Justice, J. N., Nambiar, A. M., Tchkonia, T., Lebrasseur, N. K., Pascual, R., Hashmi, S. K., … & Kirkland, J. L. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 40, 554–563. https://doi.org/10.1016/j.ebiom.2019.04.022

Onyango, A. N., & Mutua, K. (2020). The potential role of senescence in African metabolic disease profiles. African Journal of Health Sciences, 33(2), 45–58. http://ajhsjournal.or.ke/vol33issue2/senescence-metabolic.pdf

Ogunlesi, M., Okiei, W., & Azeez, L. (2020). Phytochemical and senolytic potential of selected African herbal remedies. African Journal of Traditional, Complementary and Alternative Medicines, 17(3), 14–25. https://doi.org/10.21010/ajtcam.v17i3.3

Tangwa, G. B. (2017). Bioethics in Africa: Theories and practice. Cambridge Quarterly of Healthcare Ethics, 26(3), 401–405. https://doi.org/10.1017/S0963180116001083

Xu, M., Palmer, A. K., Ding, H., Weivoda, M. M., Pirtskhalava, T., White, T. A., … & Kirkland, J. L. (2018). Targeting senescent cells enhances adipogenesis and metabolic function in old age. eLife, 7, e31203. https://doi.org/10.7554/eLife.31203