Biology subjects

Libert, S.

Publications and source records attributed to Libert, S..

3 recordsLinked to original sources

bioRxiv2026

Imageomics defines granular morphological changes of human skin with age and reveals a rejuvenating effect of xenografting

Rejuvenating aging human skin is a major therapeutic goal, but objective, quantitative measures of intrinsic aging are limited. We performed a cross-sectional histological study of UV-protected buttock and abdominal skin in adults spanning multiple decades of life to identify features that reliably track age. Epidermal thickness measured between rete ridges was unchanged, but rete ridge size declined linearly with age: ridges became shorter and thinner in both sites, though rete ridge number decreased only in the abdomen. Consistent with these structural changes, proliferative cells (Ki67+) per ridge and expression of integrin {beta}4 (ITGB4), a putative stem-cell marker, were reduced in aged skin. We combined these biomarkers into a predictive model that estimated skin age more accurately than any single marker. To test whether the model detects longitudinal change, we analyzed aged abdominal skin before and after xenografting onto young or aged mice, a procedure previously reported to rejuvenate human skin in young but not aged recipient mice. Both individual biomarkers and the imaging model indicated rejuvenation regardless of host age; however, notably, engraftment efficiency was lower in aged hosts, with surviving grafts showing younger histological phenotypes. These results provide quantitative criteria for assessing intrinsic skin aging and suggest that the process of engraftment itself is sufficient to induce rejuvenation-like changes.

pathology↗

bioRxiv2022

A Physiology Clock for Human Aging

Why people age at different rates is a fundamental, unsolved problem in biology. We created a model that predicts an individuals age from physiological traits that change with age in the large UK Biobank dataset, such as blood pressure, lung function, strength and stimulus- reaction time. The model best predicted a persons age when it heavily-weighted traits that together query multiple organ systems, arguing that most or all physiological systems (lung, heart, brain, etc.) contribute to the global phenotype of chronological age. Differences between calculated "biological" age and chronological age ({Delta}Age) appear to reflect an individuals relative youthfulness, as people predicted to be young for their age had a lower subsequent mortality rate and a higher parental age at death, even though no mortality data were used to calculate {Delta}Age. Remarkably, the effect of each year of physiological {Delta}Age on Gompertz mortality risk was equivalent to that of one chronological year. A Genome-Wide Association Study (GWAS) of {Delta}Age, and analysis of environmental factors associated with {Delta}Age identified known as well as new factors that may influence human aging, including genes involved in synapse biology and a tendency to play computer games. We identify a small number of readily measured physiological traits that together assess a persons biological age and may be used clinically to evaluate therapeutics designed to slow aging and extend healthy life.

genetics↗

bioRxiv2020

DNA repair-based classification of melanoma cell lines reveals an effect of mutations in BRAF and NRAS driver genes on DNA repair capacity

Melanoma, the most serious form of skin cancer, frequently involves the dysregulation of key signaling pathways. Treatment strategies presently target the MAPK/ERK pathway, which is overactive in melanomas due in part to BRAF and NRAS mutations, and involve inhibitors against mutated BRAF (vemurafenib or dabrafenib) or MEK kinases (cobimetinib or trametinib), or a combination of the two. Using an established biochip technology, we assessed base excision repair (BER) and nucleotide excision repair (NER) activities in a collection of BRAF mutated (A-375, Colo 829, HT-144, Malme-3M, SK-mel5, SK-mel24 and SK-mel28) and NRAS mutated (M18, MZ2 and SK-mel2) melanoma cell lines, as well as wild-type controls (A7, CHL-1). We evaluated both basal activities (i.e., without treatment) and repair capacities after treatment with vemurafenib or cobimetinib alone, or in combination. Our results indicate that globally the DNA repair capacity of the cell lines was determined by the mutation status of the BRAF and NRAS genes, indicating that the MAPK pathway participates in the regulation of both BER and NER. Treatment of BRAF mutated melanoma cells with vemurafenib alone or the vemurafenib/cobimetinib combination, but not cobimetinib alone, led to reduced DNA repair capacity in about 60% of the BRAF mutated samples, indicating that signaling pathway inhibition can alter DNA repair activity. Upregulation of some DNA repair activities was also observed in several of the treated samples, suggesting activation of compensatory signaling pathways upon treatment. The data collectively indicate that mutations in the BRAF and NRAS genes exert distinct regulatory effects on the excision/synthesis steps of the BER and NER pathways and that targeted pharmacological inactivation of the signaling mechanism can translate into specific consequences in DNA repair capacity. The heterogeneity of the responses reported herein could help define subtypes of melanoma that are associated with resistance to targeted therapies.

cancer biology↗