Many disparate aspects of aging correlate with one another, emerging from the same underlying processes of cell and tissue damage. Similarly, any one specific form of age-related damage will tend to correlate with outcomes in aging regardless of whether it makes a sizable contribution to those outcomes. There are so many bidirectional connections between forms of damage, and between consequent dysfunction and forms of damage, that excess in any one aspect of aging tends to drag along the others. Nonetheless, there are cases in which one can reasonably speculate about causation in a narrow sense of one mechanism and one outcome, as the contribution is likely large enough to consider in isolation. Here is one of them, the link between levels of the metabolic waste of advanced glycation endproducts and their relation to physical frailty.
Advanced glycation endproducts (AGEs) form non-enzymatic cross-links with proteins, thereby altering the structure of extracellular matrix proteins comprising muscles and skeletal tissues. These structural changes negatively affect tissue stiffness and elasticity. Consequently, the altered physical properties of musculoskeletal tissues reduce force transmission from the muscle fibers, resulting in a decline in muscle strength and function. Additionally, AGEs bind to the receptor for AGEs (RAGE), promoting inflammatory responses and oxidative stress, which contribute to muscle cell dysfunction and the aging of muscle cells. However, AGEs accumulation is likely a consequence rather than the initial trigger of oxidative stress and inflammation. Minor but chronic oxidative stress and proinflammatory conditions create a favorable environment for the formation of AGEs, nitrosylated proteins, and lipids, which in turn propagate oxidative damage through radical chain reactions. This bidirectional relationship between oxidative stress and AGEs suggests a reinforcing cycle rather than a one-way causative mechanism
This cross-sectional correlational study included 552 community-dwelling older adults. AGE accumulation was assessed using skin autofluorescence (SAF) measured using an AGE reader. Mobility decline factors were evaluated using the sit-to-stand (STS), gait speed (4 m walk tests), single-leg stance (SLS), and Timed Up and Go (TUG) tests. A comparison of the physical function across the quartile groups revealed that the group with the highest SAF values exhibited a general decline in STS, gait speed, SLS, and TUG performance when compared with the other groups. Spearman's correlation analysis revealed that the SAF-AGEs demonstrated significant negative correlations with STS, gait speed, and SLS. Additionally, TUG showed a significant positive correlation. In conclusion, this study has demonstrated that higher SAF values were associated with decreased lower-limb strength, gait speed, and balance, thereby suggesting that SAF may be a useful screening tool for predicting mobility decline in older adults.
Link: https://doi.org/10.3390/healthcare13060613
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