Crosstalk Between Senescent Bone Cells and the Bone Tissue Microenvironment Influences Bone Fragility During Chronological Age and in Diabetes.

Bone is a complex organ serving roles in skeletal support and movement, and is a source of blood cells including adaptive and innate immune cells. Structural and functional integrity is maintained through a balance between bone synthesis and bone degradation, dependent in part on mechanical loading but also on signaling and influences of the tissue microenvironment. Bone structure and the extracellular bone milieu change with age, predisposing to osteoporosis and increased fracture risk, and this is exacerbated in patients with diabetes.

Interconnections between Inflammageing and Immunosenescence during Ageing.

Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued presence of the initial trigger, or the dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults, including centenarians, is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death.

The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging.

The receptor for advanced glycation end-products (RAGE) was initially characterized and named for its ability to bind to advanced glycation end-products (AGEs) that form upon the irreversible and non-enzymatic interaction between nucleophiles, such as lysine, and carbonyl compounds, such as reducing sugars. The concentrations of AGEs are known to increase in conditions such as diabetes, as well as during ageing. However, it is now widely accepted that RAGE binds with numerous ligands, many of which can be defined as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs).

Knockout of receptor for advanced glycation end-products attenuates age-related renal lesions.

Pro-aging effects of endogenous advanced glycation end-products (AGEs) have been reported, and there is increasing interest in the pro-inflammatory and -fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill-defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML-enriched diet on renal aging.