Inflammatory bowel disease (IBD), a group of chronic gastrointestinal inflammatory diseases, including ulcerative colitis (UC) and Crohn's disease (CD), is an increasing clinical and public health challenge [1], [2], [3], [4]. In recent years, with the process of ageing and the lifespan increasing, the elderly is the largest growing population, which comprised at least one-third of the total IBD patients [5], [6]. It is estimated that the number of adults ≥60 years with IBD will increase greater than 200% by the year of 2030 in North America [7]. In these elderly IBD patients, two phenotypes were defined according to the age of IBD diagnosis: elderly patients who were diagnosed IBD at younger than 60 years old (adult-onset IBD), and elderly patients with IBD diagnosis at older than 60 years old (elderly-onset IBD). Several previous studies have suggested higher risks of mortality, cancer development, infections, hospitalizations in elderly-onset IBD, compared with adult-onset IBD [5], [8]. But few studies have specifically addressed the interplay between elderly-onset IBD and ageing [9].

Frailty, a decreased physiologic reserve and a consequence of biological ageing, is an emerging indicator in risk prediction in IBD [10]. The prevalence of frailty in patients with IBD was 39.3% in biologic-treated patients with IBD [11]. In addition, frailty is increasing in parallel with age, from 4% in patients aged 20-29 years to 25% in patients older than 90 years [12]. Recently, frailty has been reported to be independently associated with higher risks of infection, mortality, hospitalization, postoperative outcomes and healthcare-related costs in patients with IBD [11], [12], [13], [14], [15]. In the attempt to operationalize the definition of frailty, Fried and colleagues proposed a landmark phenotype in following 5 components: weight loss, exhaustion, impaired grip strength, slow gait speed and low physical activity. The presence of at least 3 of these features is necessary to label an individual as frail, whereas the presence of 1 to 2 features confers a label of pre-frail [16]. Following Fried, Rockwood and Mitnitski also released their accumulated deficits model of frailty, which combining the physical components and the psychosocial aspects of frailty [17]. Other measurement of frailty in research and clinical practice including the Study of Osteoporotic Fractures Index, Edmonton Frailty Scale, the Fatigue, Resistance, Ambulation, Illness and Loss of weight Index and others. Among these indicators, Fried’s frailty phenotype has achieved international reputation with extensive validation in the research literature [18].

Up to date, there is still lacking of evidence on whether frailty could increase the risk of elderly-onset IBD. Besides, it is of high priority to further identify pre-frailty earlier and examine the relationship between pre-frailty and risk of elderly-onset IBD, given the high prevalence of pre-frailty in older adults and the dynamic transition process between pre-frail and frail status. To the best of our knowledge, the association between frailty and pre-frailty, and the risk of elderly-onset IBD has not ever been thoroughly examined. Accordingly, in this study, we aimed to comprehensively investigate the long-term risk of elderly-onset IBD associated with frailty and pre-frailty in a large prospective population-based UK Biobank cohort with thousands of IBD incident cases.