The TNF-α antagonist etanerceptreverses age-related decreases in colonic SERT expression and faecal output in mice

Treatment for chronic constipation in older people is challenging and the condition has a major impact on quality of life. A lack of understanding about the causes of this condition has hampered the development of effective treatments. 5-HT is an important pro-kinetic agent in the colon. We examined whether alterations in colonic 5-HT signalling underlie age–related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. Components of the 5-HT signalling system (5-HT, 5-HIAA, SERT) and TNF-α expression were examined in the distal colon of 3, 12, 18 and 24- month old mice and faecal output and water content monitored under control conditions and following the administration of etanercept (TNF-α inhibitor; 1 mg Kg-1). Faecal output and water content were reduced in aged animals. Age increased mucosal 5-HT availability and TNF-α expression and decreased mucosal SERT expression and 5-HIAA. Etanercept treatment of old mice reversed these changes, suggesting that age-related changes in TNFα expression are an important regulator of mucosal 5-HT signalling and pellet output and water content in old mice. These data point to “anti-TNFα” drugs as potential treatments for age-related chronic constipation

Quality of life in residential care

While some of the changes in life that accompany increasing age may promote higher quality of life, the increased prevalence of disease and other negative life events presumably operate in the opposite direction. Among the most salient negative life events in later life is the development of physical or mental disability sufficiently severe 10 justify moving from an independent life in the community to a residential care facility. This chapter first reviews the current state of knowledge concerning quality of life with increasing age. Most studies note changes. but the distinction of age effects from cohort effects is not often made. Illness in later life has a major impact upon quality of life, especially if disability is one outcome. As illness and disability often lead to a move into a residential care facility, the quality of life in residential care becomes of broader interest. Such interest is enhanced by the strong contrast in views expressed by people when contemplating life in residential care and when actually experiencing it. Various models of this apparent "disability paradox" are described, followed by an analysis of the conceptual difficulties underlying research into quality of life because of the varied definitions in current use