Facing up to the Global Challenges of Ageing |
Longer human lives have led to a global burden of late-life disease However some older people experience little ill health a trait that should be extended to the general population Interventions into lifestyle including increased exercise and reduction in food intake and obesity can help to maintain healthspan Altered gut microbiota removal of senescent cells blood factors obtained from young individuals and drugs can all improve late-life health in animals Application to humans will require better biomarkers of disease risk and responses to interventions closer alignment of work in animals and humans and increased use of electronic health records biobank resources and cohort studies Kontis V et al Future life expectancy in 35 industrialised countries projections with a Bayesian model ensemble Lancet 389 1323 1335 2017 Analysis of age-specific death rates in 35 industrialized countries shows that there is a high probability that life expectancy in these countries will continue to increase during the coming decades Christensen K McGue M Petersen I Jeune B Vaupel J W Exceptional longevity does not result in excessive levels of disability Proc Natl Acad Sci USA 105 13274 13279 2008 A survey of a Danish cohort born in 1905 and followed for physical and cognitive independence from 1998 to 2005 across the age range of 92 100 years shows that lifespan extension of a population does not necessarily results in exceptional levels of disability at high ages Barnett K et al Epidemiology of multimorbidity and implications for health care research and medical education a cross-sectional study Lancet 380 37 43 2012 Analysis of Scottish health registry data from 2007 to 2012 shows a high level of multimorbidity two or more disorders in those over age 65 and a 10 15 years earlier onset of multimorbidity in people living in socio-economically deprived areas challenging the single-disease clinical framework and advocating personalized approaches Stringhini S et al Socioeconomic status and the 25 25 risk factors as determinants of premature mortality a multicohort study and meta-analysis of 1 7 million men and women Lancet 389 1229 1237 2017 A plea to include socio-economic factors into the initiative of high income WHO member states to cut mortality due to non-communicable diseases by 25 by 2025 showing in a very large prospective multi-cohort meta-analysis study the years-of-life-lost due to high alcohol intake physical inactivity current smoking hypertension diabetes obesity and low socio-economic status Ngandu T et al A 2 year multidomain intervention of diet exercise cognitive training and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people FINGER a randomised controlled trial Lancet 385 2255 2263 2015 A two-year proof-of-concept randomized clinical trial in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability FINGER in which positive results are found for a multi-domain approach diet exercise cognitive training and vascular risk monitoring compared to general health advice to prevent cognitive decline in at-risk elderly people 60 77 years of age from the general population Wei M et al Fasting-mimicking diet and markers risk factors for aging diabetes cancer and cardiovascular disease Sci Transl Med 9 eaai8700 2017 Healthy human subjects randomly allocated to a diet that mimics fasting which is low in calories sugars and protein but high in unsaturated fats as opposed to unrestricted food consumption showed reduced body weight trunk and total body fat had lower blood pressure and decreased levels of IGF-1 with more marked effects in participants at risk of disease Mannick J B et al mTOR inhibition improves immune function in the elderly Sci Transl Med 6 268ra179 2014 At doses that were well-tolerated the mTOR inhibitor RAD001 enhanced the response to the influenza vaccine in elderly volunteers by about 20 and reduced the percentage of CD4 and CD8 T lymphocytes that expressed the programmed death-1 receptor which inhibits T cell signalling and shows higher expression with increasing age Jeon O H et al Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment Nat Med 23 775 781 2017 Transection of the anterior cruciate ligament in mice caused accumulation of senescent cells in the articular cartilage and synovium and selective elimination of these cells or injection of a senolytic molecule attenuated the development of osteoarthritis reduced pain and increased cartilage development Smith P et al Regulation of life span by the gut microbiota in the short-lived African turquoise killifish eLife 6 e27014 2017 Recolonizing the gut of middle-age turquoise killifish with bacteria from young rather than middle-aged donors extends lifespan delays behavioural decline and prevents the changes in the microbiome associated with host ageing Castellano J M et al Human umbilical cord plasma proteins revitalize hippocampal function in aged mice Nature 544 488 492 2017 Treatment with human umbilical cord plasma revitalizes the hippocampus and improves cognitive function in mice which is partially driven by TIMP2 Mertens J et al Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects Cell Stem Cell 17 705 718 2015 Direct conversion of human fibroblasts into induced neurons shows that these cells retain their age-related transcriptional profiles and demonstrates the potential of direct reprogramming for in vitro modelling of ageing Fried L P et al Frailty in older adults evidence for a phenotype J Gerontol A 56 M146 M157 2001 The Fried criteria were among the earliest multi-domain definitions to index frailty including shrinking weight loss muscle weakness handgrip strength poor endurance self-reported exhaustion slowness gait speed and low physical activity kcal expended per week estimated in community-dwelling people over 65 years and this definition of frailty is now widely used in large epidemiological and clinical studies and formed the basis for the development of novel indexes to predict elderly people who have a higher risk of incidences of disease hospitalization falls disability and mortality We thank N van den Berg for help with the preparation of Fig 1 and N Chaturvedi and B J Zwaan for their critical reading of the manuscript LP acknowledges support from the European Research Council ERC under the European Unions Horizon 2020 research and innovation programme no 741989 and a Wellcome Trust Strategic Award JD acknowledges support from the Alexander von Humboldt Foundation We apologize to the authors of many relevant studies for not citing their work owing to space limitations Nature thanks V D Longo and J Vijg for their contribution to the peer review of this work All authors contributed to the design and writing of the Review The authors declare no competing interests