Trends in Endocrinology & Metabolism
ReviewInflammaging and ‘Garb-aging’
Section snippets
Aging Is Characterized by Chronic Low-Grade Inflammation
It is well established that aging is a major risk factor for all chronic diseases and geriatric syndromes [cardiovascular diseases (CVD) and neurodegenerative diseases, cancer, type 2 diabetes mellitus (T2DM), arthritis, chronic obstructive pulmonary disease, sarcopenia, frailty, among others] that negatively affect health span and longevity. Many epidemiological and biodemographic studies show that biomarkers of inflammation are robust predictors of morbidity (chronic diseases) and mortality
Inflammaging and Anti-Inflammaging: The Biological Structure of Inflammatory Markers
In most studies, inflammaging has been assessed and tested by measuring a limited number of inflammatory molecules, namely cytokines, chemokines, and acute-phase proteins, in the blood of older subjects [4]. By contrast, in the ‘InCHIANTI’ study, 19 inflammatory biomarkers were measured and principal component analysis (PCA) was used to reveal an unexpected relation among these markers [5]. The first component of the PCA was driven largely by the soluble tumor necrosis factor receptors (STNF-RI
Inflammaging and Anti-Inflammaging: The Results of Metabolomics and Lipidomics
A study involving 143 centenarians, 210 offspring of centenarians, 73 offspring of nonlong-lived parents and 21 young subjects, identified a metabolomics signature of aging and longevity involving amino acids [tryptophan (Trp), tyrosine, and phenylalanine], lysophosphatidylcholines, sphingomyelins, glycerophospholipids, and an age-related complex remodeling of arachidonic acid products with a concomitant increase in both pro-inflammatory leukotrienes and anti-inflammatory compounds (HETE and
Inflammaging and Anti-Inflammaging: The Contribution of Gut Microbiota
The age-related differences in the gut microbiota (GM) composition among young adults, older humans, and centenarians, were recently explored [15]. It was observed that, in centenarians, the GM is characterized by a rearrangement in the Firmicutes population, an enrichment in facultative anaerobes, notably ‘pathobionts’ (i.e., opportunistic proinflammatory bacteria generally present in the adult gut ecosystem in low numbers), and a marked decrease in Faecalibacterium prauznitzii and its
Inflammaging within the New Perspective of Geroscience
Over the past 10–15 years, a consistent and coherent literature has accumulated suggesting that, beyond the immune system, a variety of organs, tissues, and cells, including skeletal muscle and adipose tissue (AT), are capable of producing proinflammatory compounds [19]. Within this perspective, inflammaging should be considered a multifactorial, multiorgan, and systemic process, characterized by complex interactions of a plethora of molecular mediators within a larger network of basic
Where Do the Stimuli Fuelling Inflammaging Come From?
Previous research suggested that inflammatory stimuli that trigger and sustain inflammaging largely derive from long-lasting exposure to persistent viral infections and are modulated by one's own clinical history (‘immune biography’) [21]. A large body of evidence indicates cellular debris and misplaced and/or misfolded self-molecules as important and perhaps dominant players in such a process (Figure 1). In fact, persistent viral infections appear to be dispensable, at least in part, in the
Inflammaging and Misplaced Self-Molecules
When cells actively proliferate, end-products of metabolism and catabolism, as well as damaged or dysfunctional proteins, become diluted into daughter cells; however, in nonproliferating cells, such as neurons, they can accumulate in vivo until a crucial threshold is reached, after which the cells die [43]. These products include lipofuscins, advanced glycation end-products (AGEs), Tau protein aggregates, alpha-synuclein fibrils, and beta-amyloid networks. All these products can be recognised
Propagation of Inflammaging: The Communicomes
Local and systemic inflammaging favors the onset of chronic diseases when additional determinants (genetic risk variants, unhealthy lifestyle, and early events favoring inflammation with late effects in adult and old age) are involved. It is likely that chronic diseases accelerate organismal aging in a vicious cycle that is difficult to stop [26]. In favor of this assumption, several data suggest that cell senescence propagates from cell to cell via a bystander effect (‘senescence-induced
Concluding Remarks and Future Perspectives
The search for the final determinants of aging is an endless quest. The link between chronic stress, the microbiota–gut–brain axis, and increased inflammatory state is emerging as a unified body–brain–mind framework that can be used to understand aging and age-related diseases [81]. We propose here a unifying perspective that has the potential to form a coherent framework of the fragmented pieces of evidence published in diverse fields from apoptosis, cell death, and cancer, to obesity. In its
Acknowledgments
This work was supported by the European Union (EU)’s H2020 Project ‘Propag-ageing’ (grant agreement no. 634821) to C.F. and P.G.; EU JPND ‘Adage’ to C.F., EU FP7 NU-AGE (grant agreement no. 266486) to C.F. and University of Bologna FARB linea 2 Project 2014 no. RFBO120790 to M.C.
Glossary
- Communicome
- a term coined by Tony Wyss-Coray [73] to indicate the proteins that carry information from one cell to another. In this review, ‘communicome’ is used to indicate all the molecules (not exclusively proteins) actively secreted or passively released in the blood stream. We intend that every organ and/or tissue has its own ‘communicome’, which can differ (totally or partially) from that of other organs and/or tissues.
- ‘Garbage’
- used here to indicate all the cellular and molecular products
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