Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function

Frontiers in Neuroscience

Joanne Chin-Aleong¹  Charles H. Knowles¹  Joanne E. Martin¹  Sarah Epton¹  Luke Gammon²  Cleo L. Bishop³  Ellie Crawley⁴  Shezan Elahi⁴  Gareth J. Sanger⁴  Yichen Xu⁴  Marilisa Straface⁴  Alexandra Palmer⁴  Meghan M. Edgar⁵ 

[1] Barts Health NHS Trust, Department of Colorectal Surgery and Pathology, The Royal London Hospital, London, United Kingdom;Center for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;Center for Inflammation and Therapeutic Innovation Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;Center for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom;Gastroenterology Drug Discovery Unit, Takeda Pharmaceuticals, San Diego, CA, United States;

关键词: senescence;    p16;    aging;    human;    colon;    myenteric neuron;   

DOI  :  10.3389/fnins.2021.747067

来源: DOAJ

【 摘 要 】

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.

【 授权许可】

Unknown