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Senescence and Age-related Disease: A systematic review and meta-analysis

S. Luesken (1, 2), C. Tuttle (2), M. Waaijer (3) and A. Maier (2, 4)

  1. Selective Utrecht Medical Master, UMC Utrecht, Utrecht University, Utrecht, the Netherlands

  2. @AgeMelbourne, Department of Medicine and Aged Care, University of Melbourne, Melbourne, Victoria, Australia

  3. Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands

  4. @AgeAmsterdam, Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, The Netherlands

Background

Cellular senescence has been associated with chronological age, biological age and age-related diseases. However, whether senescent cells are higher at sites of pathology within humans remains inconclusive. In this review and meta-analysis, we aimed to determine if known markers of senescence are higher at sites of pathology within diseased subjects compared to healthy controls.

Methods

A systematic review of the databases; PubMed, EMBASE and Web of Science was performed to isolate articles investigating a relationship between cellular senescence and age-related diseases within humans. Articles that utilised an in vitro design were excluded from this review. A meta-analysis using pooled standardized mean differences (SMD) of senescence markers within tissue of disease subjects and healthy controls was performed. The analysis was further sub grouped by disease, tissue/cell type and senescence marker.


Results

Overall 60 articles met inclusion criteria for this review of which 42 articles (n = 4326) could be included in the meta-analysis. The meta-analysis identified higher levels of senescence markers in tissue samples from subjects with cardiovascular and metabolic (SMD: 1.98, 95% CI = 1.16-2.80), respiratory (SMD: 1.81, 95% CI = 0.78-2.83), kidney (SMD: 2.29, 95% CI = 1.21-3.37) and eye diseases (SMD: 1.71, 95% CI = 0.72-2.70) compared to healthy controls. On the other hand, subjects with brain diseases had lower levels of senescence markers compared to healthy controls (SMD: 0.47, 95% CI = -0.01 - 0.97).


Conclusion

This study confirms that senescence markers are higher in tissues from subjects with age-related diseases, compared to healthy controls. However, the level of senescence within tissue maybe specific to certain disease pathologies.