Senescence in tissue samples of humans with age-related diseases: A systematic review

•Higher numbers of senescent cells have been implicated in age-related diseases.•In humans, senescence is most studied in the heart and the respiratory system.•The cell cycle regulator p16ink4a is most often investigated.•Higher numbers of senescent cells are observed in human diseased tissues.•The higher expression is independent of the marker used to detect senescence. Higher numbers of senescent cells have been implicated in age-related disease pathologies. However, whether different diseases have different senescent phenotypes is unknown. Here we provide a systematic overview of the current available evidence of senescent cells in age-related diseases pathologies in humans and the markers currently used to detect senescence levels in humans. PubMed, Web of Science and EMBASE were systematically searched from inception to the 29th of September 2019, using keywords related to ‘senescence’, ‘age-related diseases’ and ‘biopsies’. In total 12,590 articles were retrieved of which 103 articles were included in this review. The role of senescence in age-related disease has been assessed in 9 different human organ system and 27 different age-related diseases of which heart (27/103) and the respiratory systems (18/103) are the most investigated. Overall, 27 different markers of senescence have been used to determine cellular senescence and the cell cycle regulator p16ink4a is most often used (23/27 age-related pathologies). This review demonstrates that a higher expression of senescence markers are observed within disease pathologies. However, not all markers to detect senescence have been assessed in all tissue types.