News in Brief
Authors: Rebecca Barksby
Journal: The Lancet Healthy Longevity (2021)

Inherited genes affect an individual's risk of developing many diseases, but how this genetic risk changes as we age is relatively unknown. A study using a proportional hazards model by Xilin Jiang (University of Oxford, Oxford, UK) and colleagues aimed to assess the extent that genetics affect disease susceptibility throughout life. Using genomic data from the UK Biobank, researchers analysed the genetic risk of developing 24 common diseases for 409 694 people with British Isles ancestry. Nine diseases (hypertension, skin cancer, atherosclerosis, hypothyroidism, calculus of gallbladder, hypercholesterolaemia, angina, and myocardial infarction) showed that genetic risk had smaller effect sizes with increasing age. For example, the genetic effect on atherosclerosis risk was found to be higher in the youngest (<45 years) age group (OR for 90th percentile of genetic risk 3·63, 95% CI 3·47–3·79) than in the oldest (>75 years) age group (1·77, 1·67–1·88). However, the extent of this decline varies for each disease. By comparison, for hypercholesterolemia, the greatest decrease in genetic risk was between the two youngest (<45 years and 45–50 years) age groups (2·21, 2·12–2·30 vs 1·63, 1·58–1·69). The authors attribute this decline of the genetic effect to non-genetic risk covariates (such as environmental factors) that accumulate and mitigate genetic risk over time. However, the authors emphasise that this effect does not mean that polygenic risk scores are not relevant for predicting disease in older age. Rather, the results show that genetic risk among individuals can change over time and that age should be considered when determining disease profiles. The authors hope that this study will prompt research on the clinical consequences of age-varying genetic risk. 400 000 older people live in care homes in the UK and it is projected that this population will increase by 127% over the next 20 years. To provide quality care for this ageing population, the British Geriatrics Society (BGS) has published 11 recommendations for the care home sector. Offering patient-centred care is a key theme within the 13-page document and the BGS calls for routine use of Comprehensive Geriatric Assessment (CGA) for every older person entering a care home. A current problem with CGA, say the BGS, is that there is no standard definition of a multidisciplinary team, meaning that CGA is not uniformly applied and recorded. The BGS calls for the definition of the multidisciplinary team to be developed and standardised and recommends that members undergo specific training in the care of older people and have defined core competencies. The recommendations follow on from the publication of BGS guidance for COVID-19 care. According to the BGS, the COVID-19 pandemic highlighted major flaws within the UK care system. 37% of COVID-19 deaths in the UK were care home residents, however, the BGS states that the exact number is unknown because data availability and sharing between care homes is currently inadequate. To address this issue, the BGS has three data-based recommendations for the UK Government: secure investment for digital technology, develop linked datasets, and educate staff to use these technologies. The BGS hopes that applying these recommendations during the anticipated reform of social care will ensure that older people living in care homes in the UK will have access to high-quality care. Exercise has protective effects against cognitive decline in ageing. The FNDC5 protein is a key regulator of these cognitive benefits, but it is unknown whether its secreted hormone, irisin, can sustain these benefits alone. In a preclinical gene knockout study, led by Christiane Wrann (Massachusetts General Hospital, Harvard Medical School, Bostin, MA, USA) and colleagues, genetic deletion of Fndc5 was used to assess the effect of irisin on cognitive function in mice. Researchers exercised wildtype (WT-run; n=12) and Fndc5-knockout (KO-run; n=14) mice and compared their cognitive function with sedentary wildtype (WT-sed; n=9) and Fndc5KO (KO-sed; n=12) mice. The WT-run group unsurprisingly performed better in memory tests than their sedentary equivalents. However, the KO-run group did not perform significantly better than the WT-sed group. When aged, the Fndc5KO mice showed significantly more cognitive decline than the Fndc5WT mice. Additionally, Fndc5KO mice had 37% less long-term potentiation than Fndc5WT mice after 1 h of high-frequency stimulation—ie, deletion of Fndc5 impairs cognitive function in exercise and ageing. Researchers crossed Fndc5KO mice with Alzheimer's disease mice models. These hybrid mice performed worse on cognitive tests than the Alzheimer's disease models and showed significantly higher concentrations of soluble Aβ-40, a biomarker for plaque formation. Importantly, treatment with peripheral irisin, which elevates irisin blood concentrations, improved cognitive function and reduced glia activation in two Alzheimer's disease mice models. Peripheral irisin crossed the blood–brain barrier, suggesting that it could have therapeutic effects on neurodegeneration. For Islam and colleagues' study see Nat Metab 2021; 3: 1058–70For British Geriatrics Society document see https://www.bgs.org.uk/resources/ambitions-for-change-improving-healthcare-in-care-homesFor Jiang and colleague's study see PLOS Genetics 17: e1009723 For Islam and colleagues' study see Nat Metab 2021; 3: 1058–70 For British Geriatrics Society document see https://www.bgs.org.uk/resources/ambitions-for-change-improving-healthcare-in-care-homes For Jiang and colleague's study see PLOS Genetics 17: e1009723