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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.
Ferrucci, L, Fabbri, E
Nature reviews. Cardiology. 2018;15(9):505-522
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Plain language summary
Inflammageing is a term used to describe elevated blood inflammatory markers that leads to frailty and increases an individual’s risk for heart disease, kidney disease and other physical and mental illnesses. Whether inflammageing is causal in heart disease is still uncertain. This large review of 310 papers aimed to understand the causes and role of inflammageing in heart disease and other illnesses associated with ageing. Causes of inflammageing were discussed and mechanisms are not fully understood. Genetic susceptibility, obesity, gut microbiota, gut permeability, when cells can no longer divide, and chronic infections were all implicated. The role of inflammageing in heart disease was a focus and the authors deduced that it was likely to be both causal and a result of heart disease. However, the administration of anti-inflammatories in heart disease has not always proved a successful treatment. Possible causes of inflammageing are likely to be linked and cumulative and although inflammation may cause age related diseases, its role in protecting the body means that its benefits outweigh its consequences. It was concluded that controlling inflammageing may prevent heart disease and other diseases associated with ageing. This study could be used by healthcare professionals to help understand what inflammageing is and its role in age related diseases.
Abstract
Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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Gut dysbiosis: a potential link between increased cancer risk in ageing and inflammaging.
Biragyn, A, Ferrucci, L
The Lancet. Oncology. 2018;19(6):e295-e304
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This study looks at the important role our gut bacterial and commensal microbes play in supporting immunity and potentially reducing the risk of cancer from aging. Cancer risk increases as we age and is one of the main causes of reduced life expectancy. Our gut microbiome changes continually in response to diet, lifestyle, infection, and activation of immune responses. Gut dysbiosis is characterised by a shift towards proinflammatory commensals and a reduction of beneficial microbes, which can cause impairment and leakiness of the intestinal barrier. This is thought to trigger inflammaging or rather aging in a state of continual inflammation, where the immune system is in a heightened state of activation, and the body essentially creates an environment conducive to cancer. The gut is populated by trillions of species of bacteria which work together with our immune cells. As we age the diversity and density of these beneficial bacteria reduce. Therapies which support the balance of our commensal bacteria may prove effective at reducing rates of cancer in the elderly.
Abstract
Cancer incidence substantially increases with ageing in both men and women, although the reason for this increase is unknown. In this Series paper, we propose that age-associated changes in gut commensal microbes, otherwise known as the microbiota, facilitate cancer development and growth by compromising immune fitness. Ageing is associated with a reduction in the beneficial commensal microbes, which control the expansion of pathogenic commensals and maintain the integrity of the intestinal barrier through the production of mucus and lipid metabolites, such as short-chain fatty acids. Expansion of gut dysbiosis and leakage of microbial products contributes to the chronic proinflammatory state (inflammaging), which negatively affects the immune system and impairs the removal of mutant and senescent cells, thereby enabling tumour outgrowth. Studies in animal models and the importance of commensals in cancer immunotherapy suggest that this status can be reversible. Thus, interventions that alter the composition of the gut microbiota might reduce inflammaging and rejuvenate immune functions to provide anticancer benefits in frail elderly people.