Properties of the extracellular matrix that supports cells change with age. Increased stiffness is common in many tissues as a result of chemical cross-linking and other changes. Researchers here report on a proof of concept in vitro study in which increased stiffness of the local matrix is shown to promote gene expression changes in cells characteristic of aging. Reducing the stiffness reverses those changes. So one might argue that ways to repair the extracellular matrix in living tissues could rejuvenate cell behavior and tissue function to some degree.
While the development of ever more sophisticated artificial extracellular matrix materials is a notable part of the field of tissue engineering, efforts to modify the natural extracellular matrix in living tissues are not well funded, and little progress has been made in those areas in which benefits are thought likely, such as finding ways to remove age-related accumulation of cross-links. Indeed, many aspects of the chemistry of the aged extracellular matrix are not well understood, and it is far from clear as to which of the many possible approaches will yield the most useful results if successful.
Aging involves the accumulation of molecular alterations within cells and the extracellular matrix, resulting in cellular senescence and declining physiological functions. This study investigates the correlation between the biophysical environment and cellular aging, specifically examining how mechanical and biochemical cues affect cellular senescence and tissue degeneration. Cells were cultured on acrylamide hydrogels of different stiffnesses (4 and 19 kPa), and their mechanical properties were characterized by measuring Young's modulus via compression tests. Cell proliferation, morphology, gene and protein expression, and autophagy activity were assessed using multiple assays and imaging techniques.
Cells cultured on stiff hydrogels exhibited elongated morphologies, whereas cells on soft hydrogels formed spherical clusters. Notably, longevity-associated genes were upregulated in cells cultured on softer substrates. Reversibility experiments demonstrated that the aging phenotype could be reversed by modulating mechanical culture conditions, with softer environments enhancing autophagic activity. In summary, hydrogel stiffness significantly impacts aging-related cellular behavior. These findings suggest biomechanical cues as a promising strategy to promote cellular rejuvenation and combat aging.
Link: https://doi.org/10.3390/cells15151380
View the full article at FightAging
