Yaşlanma Süreciyle Gastrointestinal Sistemde Gelişen Bazı Fonksiyonel Değişimlerin Mekanizması
Özet
Yaşlanmayla birlikte iştahsızlığın gelişiminde olduğu gibi bazı fonksiyonel değişimlere öncülük eden farklılaşmalar olmaktadır. Oral ile faringeal aşama arasındaki gecikmede artış, aspirasyon riskiyle birliktedir. İleri yaşlarda, özofagus peristaltizminde ve alt özofageal sfinkter basıncında azalma gelişmektedir. Mide boşalmasında yavaşlama eğilimi, postprandial hipotansiyona ve sindirim bozukluğuna öncülük etmektedir. İnce bağırsak geçiş süresinde ise azalma olmaktadır. Kolonda itici etkinlik azalmakta, kabızlık insidansı artmaktadır. Kolonik kas duvarının yaşla zayıflaması, divertiküloz gelişimine öncülük edebilmektedir. Yaşlanmayla birlikte, anorektumdaki fonksiyonel değişiklikler sonucunda fekal inkontinans gelişebilmektedir.
Enterik nöronların sayısında yaşla azalma, özellikle miyenterik pleksusta nöron kaybı meydana gelmekte, insan kolonu ve ileumda miyenterik ganglionların önemli bir kısmında gangliyonlarda boşluklar artmaktadır. Ayrıca, yaşlı farelere ait miyenterik pleksuslarda, barsak düz kaslarını uyaran kolin asetil transferaza sahip nöronların ve barsak düz kaslarını baskılayan nitrik oksit sentaz üreten nöronların azaldığı gösterilmiştir.
Bağırsak mikrobiyotasında bakteri metabolitlerinden olan kısa zincirli yağ asitleri, nöronal aktiviteyi modüle edebilir ve anti-inflamatuar etkiye sahiptir. Bununla birlikte, yaşlanmayla disbiosis gelişebilmekte ve mikrobiyal kaynaklı metabolitleri etkileyen proteolitik bakterilerin artışı görülmektedir.
Genomik stabilitenin devamlılığında ve hücresel strese yanıtta rolleri olan sirtuinlerden (SIRT), SIRT1’ün barsak epitelinde deneysel olarak yokluğunun, artmış inflamasyon ve değişmiş barsak mikrobiomuyla birlikte olduğu bilinmektedir.
The differentiations with aging lead to some functional changes, such as development of anorexia. The delay between oral and pharyngeal stages is associated with the risk of aspiration. In elderly ages, a decrease in esophageal peristalsis and lower esophageal sphincter pressure develops. The tendency of slow gastric emptying leads to postprandial hypotension and digestive disorders. However, there is a reduction in small intestine transit time. The propulsive activity in colon decreases and the incidence of constipation increases. The weakening of colonic muscle wall can lead to the development of diverticulosis. Fecal incontinence may also is a result of functional changes in anorectum.
The number of enteric neurons decreases with age, neuron loss occurs especially in myenteric plexus and gaps increase in a significant portion of myenteric ganglia in human colon and ileum. It has also been shown that neurons with choline acetyltransferase which stimulates intestinal smooth muscle and neurons producing nitric oxide synthase which suppresses intestinal smooth muscle are reduced in myenteric plexuses of aged mice.
Short-chain fatty acids which are bacterial metabolites in intestinal microbiota can modulate neuronal activity and have anti-inflammatory effects. However, dysbiosis can develop with aging and proteolytic bacteria affects microbial metabolites.
The sirtuins (SIRTs) play a role in maintenance of genomic stability and response to cellular stress. It is known that experimental absence of SIRT1 in intestinal epithelium is associated with increased inflammation and altered intestinal microbiome.
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