Related Experiment Video
Updated: Dec 26, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Survey of senescent cell markers with age in human tissues
M Laura Idda1,2, Waverly G McClusky1, Valeria Lodde1,3
1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Abstract:
Cellular senescence, triggered by sublethal damage, is characterized by indefinite growth arrest, altered gene expression patterns, and a senescence-associated secretory phenotype. While the accumulation of senescent cells during aging decreases tissue function and promotes many age-related diseases, at present there is no universal marker to detect senescent cells in tissues. Cyclin-dependent kinase inhibitors 2A (p16/CDKN2A) and 1A (p21/CDKN1A) can identify senescent cells, but few studies have examined the numbers of cells expressing these markers in different organs as a function of age. Here, we investigated systematically p16- and p21-positive cells in tissue arrays designed to include normal organs from persons across a broad spectrum of ages. Increased numbers of p21-positive and p16-positive cells with donor age were found in skin (epidermis), pancreas, and kidney, while p16-expressing cells increased in brain cortex, liver, spleen and intestine (colon), and p21-expressing cells increased in skin (dermis). The numbers of cells expressing p16 or p21 in lung did not change with age, and muscle did not appear to have p21- or p16-positive cells. In summary, different organs display different levels of the senescent proteins p16 and p21 as a function of age across the human life span.
Insights
Cellular senescence markers p16 and p21 increase with age in various human organs, but not uniformly. This study quantifies these senescent cells across different tissues, revealing organ-specific aging patterns.
Area of Science:
- Gerontology
- Cell Biology
- Pathology
Background:
- Cellular senescence is a state of irreversible growth arrest linked to aging and age-related diseases.
- Accumulation of senescent cells impairs tissue function.
- Currently, no universal marker exists for detecting senescent cells in human tissues.
Purpose of the Study:
- To systematically investigate the age-dependent changes in senescent cell markers p16 (CDKN2A) and p21 (CDKN1A) in various human organs.
- To determine if p16 and p21 expression levels vary across different tissues with age.
Main Methods:
- Utilized tissue arrays containing normal organs from individuals across a wide age range.
- Quantified the number of p16-positive and p21-positive cells in different organs.
- Analyzed the relationship between cell counts and donor age.
Main Results:
- Increased p16 and p21 positive cells were observed with age in skin (epidermis), pancreas, and kidney.
- p16-expressing cells increased with age in brain cortex, liver, spleen, and intestine (colon).
- p21-expressing cells increased in skin (dermis); lung showed no age-related changes, and muscle lacked detectable p16/p21 positive cells.
Conclusions:
- Different human organs exhibit distinct age-related accumulation patterns of senescent cells, as indicated by p16 and p21 expression.
- The findings highlight organ-specific differences in cellular senescence during aging.
- Understanding these patterns is crucial for addressing age-related tissue dysfunction and disease.
