Abstract

A plethora of factors have been attributed to underly aging, including oxidative stress, telomere shortening and cellular senescence. Several studies have shown a significant role of the cyclin-dependent kinase inhibitor p16ink4a in senescence and aging. However, its expression in development has been less well documented. Therefore, to further clarify a potential role of p16 in development and aging, we conducted a developmental expression study of p16, as well as of p19ARF and p21, and investigated their expression on the RNA level in brain, heart, liver, and kidney of mice at embryonic, postnatal, adult, and old ages. P16 expression was further assessed on the protein level by immunohistochemistry. Expression of p16 was highly dynamic in all organs in embryonic and postnatal stages and increased dramatically in old mice. Expression of p19 and p21 was less variable and increased to a moderate extent at old age. In addition, we observed a predominant expression of p16 mRNA and protein in liver endothelial cells versus non-endothelial cells of old mice, which suggests a functional role specifically in liver endothelium of old subjects. Thus, p16 dynamic spatiotemporal expression might implicate p16 in developmental and physiological processes in addition to its well-known function in the build-up of senescence.

Highlights

  • Academic Editor: Antonio PaoloAging is characterized by the gradual continuous decline of functions of cells, tissues, and the whole organism [1]

  • In addition to quantitative p16 assessment on the mRNA level, we investigated its expression in the brain, heart, kidneys, and liver at the different time points by immunohistochemistry

  • Our results have shown dynamic and differential expression of p16 during embryonic and postnatal development as well as in adult and old mice in the brain, heart, kidneys, and liver

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Summary

Introduction

Academic Editor: Antonio PaoloAging is characterized by the gradual continuous decline of functions of cells, tissues, and the whole organism [1]. In mammals, aging is associated with a variety of pathologies and has been classified as the leading predictive factor of many chronic diseases that account for the majority of morbidity and mortality worldwide [3]. These diseases include neurodegenerative (Alzheimer’s and Parkinson), cardiovascular, pulmonary, renal, and bone disorders, and cancers [4,5,6,7,8,9]. This includes oxidative stress and overproduction of reactive oxygen species, overproduction of inflammatory cytokines, activation of oncogenes, DNA damage, telomere shortening, and, accumulation of senescent cells [10,11,12,13,14,15]

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