Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity. Pep 14 functions via modulation of PP2A, an understudied holoenzyme that promotes genomic stability and is involved in DNA repair and senescence pathways. At the single-cell level, Pep 14 modulates genes that prevent senescence progression by arresting the cell cycle and enhancing DNA repair, which consequently reduce the number of cells progressing to late senescence. When applied on aged ex vivo skin, Pep 14 promoted a healthy skin phenotype with structural and molecular resemblance to young ex vivo skin, decreased the expression of senescence markers, including SASP, and reduced the DNA methylation age. In summary, this work shows the safe reduction of the biological age of ex vivo human skins by a senomorphic peptide.

Individuals with chronic kidney disease (CKD) experience physiological changes that likely impair salt taste function and perception. Sodium restriction is a cornerstone of CKD management but dietary sodium plays an important role in food enjoyment and may interfere with compliance to this intervention. Therefore, confirming that taste deficits are present in CKD will improve our understanding of how taste deficits can affect intake, and inform dietary counselling in the future. A systematic review was conducted. Studies that included adults with CKD and healthy controls, and assessed salt taste sensitivity, perceived intensity, and/or hedonic ratings were included. Study quality was assessed using the Academy of Nutrition and Dietetics Evidence Analysis Library Quality Criteria Checklist: Primary Research. Of the 16 studies, the majority reported decreased salt taste sensitivity, but no consistent differences in intensity or hedonic ratings were observed. Higher recognition thresholds in CKD patients were associated with higher sodium intake, but results should be interpreted with caution as the measures used were subject to error in this population. In conclusion, salt taste sensitivity is decreased in CKD, but intensity and hedonic evaluations appear to be more robust. Given that hedonic assessments are better predictors of intake, and that salt taste preferences can be changed over time, dietary counselling for low-sodium intake is likely to be effective for this population.

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