Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Ferrucci, Luigi; Fabbri, Elisa

doi:10.1038/s41569-018-0064-2

Cited by 1,849 publications

(1,302 citation statements)

References 308 publications

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“…S7) and 14% shorter time to developing two or more age-related morbidities ( Fig. S8), which is consistent with previous findings from the InCHIANTI study [95][96][97][98]. Our findings support the importance of chronic inflammation as a phenotypic marker of ageing and provide a potential explanation for results from the CANTOS trial, a trial investigating the effect of a monoclonal antibody targeting at interleukin-1b, where the allcause mortality did not differ between groups over a follow-up of 3.7 years, indicating longer term follow-up may be warranted.…”

Section: Discussionsupporting

confidence: 90%

A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging

et al. 2020

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Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross‐sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age‐related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixed‐effects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.

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Section: Discussionsupporting

confidence: 90%

A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging

et al. 2020

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“…For example, while the condition of “frailty” in older persons is often defined as a “reduction of physiological compensation,” almost all criteria currently proposed are based on measures of damage. Damage only emerges clinically when compensatory mechanisms are exhausted (Ferrucci & Fabbri, ). As shown in Figure , physical decline, cognitive decline, and frailty may result from two interrelated mechanisms, one inducing and the other preventing damage, which may act separately or jointly.…”

Section: Introductionmentioning

confidence: 99%

Measuring biological aging in humans: A quest

et al. 2019

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The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.

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“…Most recently, the IL‐1β antagonist canakinumab (The CANTOS trial) has been shown to be effective in preventing cardiovascular events (Ridker et al., ). There are several other clinical trials that are ongoing; for a full review, see Ferrucci & Fabbri ().…”

Section: Interventional Evidence Linking Inflammation and Age‐relatedmentioning

confidence: 99%

“…There are several other clinical trials that are ongoing; for a full review, see Ferrucci & Fabbri (2018).…”

Section: Interventional Evidence Linking Inflammation and Age-relatedmentioning

confidence: 99%

Inflammation as a mediator of arterial ageing

Trott

Fadel

2019

Experimental Physiology

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New Findings What is the topic of this review?This review summarizes and synthesizes what is known about the contribution of inflammation to age‐related arterial dysfunction. What advances does it highlight?This review details observational evidence for the relationship of age‐related inflammation and arterial dysfunction, insight from autoimmune inflammatory diseases and their effects on arterial function, interventional evidence linking inflammation and age‐related arterial dysfunction, insight into age‐related arterial inflammation from preclinical models and interventions to ameliorate age‐related inflammation and arterial dysfunction. Abstract Advanced age is a primary risk factor for cardiovascular disease, the leading cause of death in the industrialized world. Two major components of arterial ageing are stiffening of the large arteries and impaired endothelium‐dependent dilatation in multiple vascular beds. These two alterations are major contributors to the development of overt cardiovascular disease. Increasing inflammation with advanced age is likely to play a role in this arterial dysfunction. The purpose of this review is to synthesize what is known about inflammation and its relationship to age‐related arterial dysfunction. This review discusses both the initial observational evidence for the relationship of age‐related inflammation and arterial dysfunction and the evidence that inflammatory autoimmune diseases are associated with a premature arterial ageing phenotype. We next discuss interventional and mechanistic evidence linking inflammation and age‐related arterial dysfunction in older adults. We also attempt to summarize the relevant evidence from preclinical models. Lastly, we discuss interventions in both humans and animals that have been shown to ameliorate age‐related arterial inflammation and dysfunction. The available evidence provides a strong basis for the role of inflammation in both large artery stiffening and impairment of endothelium‐dependent dilatation; however, the specific inflammatory mediators, the initiating factors and the relative importance of the endothelium, smooth muscle cells, perivascular adipose tissue and immune cells in arterial inflammation are not well understood. With the expansion of the ageing population, ameliorating age‐related arterial inflammation represents an important potential strategy for preserving vascular health in the elderly.

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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Cited by 1,849 publications

References 308 publications

A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging

A roadmap to build a phenotypic metric of ageing: insights from the Baltimore Longitudinal Study of Aging

Measuring biological aging in humans: A quest

Inflammation as a mediator of arterial ageing

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