The human colon: Evidence for degenerative changes during aging and the physiological consequences

Abstract Background The incidence of constipation increases among the elderly (>65 years), while abdominal pain decreases. Causes include changes in lifestyle (e.g., diet and reduced exercise), disease and medications affecting gastrointestinal functions. Degenerative changes may also occur within the colo‐rectum. However, most evidence is from rodents, animals with relatively high rates of metabolism and accelerated aging, with considerable variation in time course. In humans, cellular and non‐cellular changes in the aging intestine are poorly investigated. Purpose To examine all available studies which reported the effects of aging on cellular and tissue functions of human isolated colon, noting the region studied, sex and age of tissue donors and study size. The focus on human colon reflects the ability to access full‐thickness tissue over a wide age range, compared with other gastrointestinal regions. Details are important because of natural human variability. We found age‐related changes within the muscle, in the enteric and nociceptor innervation, and in the submucosa. Some involve all regions of colon, but the ascending colon appears more vulnerable. Changes can be cell‐ and sublayer‐dependent. Mechanisms are unclear but may include development of “senescent‐like” and associated inflammaging, perhaps associated with increased mucosal permeability to harmful luminal contents. In summary, reduced nociceptor innervation can explain diminished abdominal pain among the elderly. Degenerative changes within the colon wall may have little impact on symptoms and colonic functions, because of high “functional reserve,” but are likely to facilitate the development of constipation during age‐related challenges (e.g., lifestyle, disease, and medications), now operating against a reduced functional reserve.