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A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21 Cip1 (p21 high) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21 high cells improves physical function at all remaining stages of life, suggesting healthspan extension. Mechanistically, p21 high cells encompass several cell types with a relatively conserved proinflammatory signature. Clearance of p21 high cells reduces inflammation and alleviates age-related transcriptomic signatures of various tissues. These findings demonstrate the feasibility of healthspan extension in mice and indicate p21 high cells as a therapeutic target for healthy aging. [Display omitted] • p21 high cells, distinct from p16 high cells, accumulate in various tissues with aging • Intermittent p21 high cell clearance extends both median and maximum lifespans in mice • Intermittent p21 high cell clearance results in sustained health improvement • Intermittent p21 high cell clearance alleviates age-related transcriptomic signatures Wang et al. identify a distinct senescent cell population (p21 high cells) in various tissues with aging. p21 high cells encompass numerous cell types with a conserved proinflammatory signature. Intermittent clearance of p21 high cells reduces inflammation, extends lifespan, and results in sustained benefits to health and physical function in old mice. [ABSTRACT FROM AUTHOR]

Hydrogels with or without chemical cross-linking have been studied and used for biomedical applications, such as tissue repair, surgical sealants, and three dimensional biofabrication. These materials often undergo a physical sol–gel or gel–sol transition between room and body temperatures and can also be chemically cross-linked at these temperatures to give dimensional stability. However, few studies have clearly shown the effect of heating/cooling rates on such transitions. Moreover, only a little is known about the effect of cross-linking temperature or the state on the modulus after cross-linking. We have established rheological methods to study these effects, an approach to determine transition temperatures, and a method to prevent sample drying during measurements. All the rheological measurements were performed minimizing the normal stress build-up to compensate for the shrinking and expansion due to temperature and phase changes. We chemically modified gelatin to give gelatin methacryloyl and determined the degree of methacryloylation by proton nuclear magnetic resonance. Using the gelatin methacryloyl as an example, we have found that the gel state or lower temperature can give more rigid gelatin-based polymers by cross-linking under visible light than the sol state or higher temperature. These methods and results can guide researchers to perform appropriate studies on material design and map applications, such as the optimal operating temperature of hydrogels for biomedical applications. We have also found that gelation temperatures strongly depend on the cooling rate, while solation temperatures are independent of the heating rate. [ABSTRACT FROM AUTHOR]