Researchers in Spain have reported new insights into how key cells in the skin lose their identity as the body ages, and say their findings could potentially lead to new dietary or other approaches to holding back the effects of time on skin cell aging and its to function normally and repair.

Studies in mice by scientists at the Institute for Research in Biomedicine (IRB Barcelona) and the Centro Nacional de Análisis Genómico of the Center for Genomic Regulation (CNAG-CRG) indicated that the dermal fibroblasts effectively ‘forget’ what they are as they age. The cells produced less of the proteins that make up the skin’s dermis, and developed traits that were characteristic of adipocytes (fat cells). “This leads to them losing their cell identity and they also stop producing and secreting collagen like they should,” commented Marion Salzer, first author of the team’s published paper in Cell.

The researchers’ studies also found that a calorie-restricted (CR) diet can delay transcriptional changes that are associated with dermal fibroblast aging, whereas a high-fat diet (HFD) appeared to speed these changes. “Our results, therefore, indicate that loss of cell identity is a previously over-looked mechanism underlying cellular aging and offer therapeutic possibilities to delay skin aging through dietary and metabolic interventions,” they concluded, in a paper titled, “Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.”

The function of many body tissues declines as we age, and this decline impacts on everyday maintenance and healing, the authors write. Dermal fibroblasts are key for the production of collagen and extracellular matrix (ECM) proteins that make up the dermis and that support the skin’s barrier function. Dermal fibroblast function is also crucial for repairing skin damage. As we age, however, the ability of fibroblasts to produce collagen declines, and so the skin heals less well.

“The elderly face many problems in this regard because their skin does not heal properly and its barrier properties are decreased, thus increasing the risk of skin infections and systemic infections,” explained research head Salvador Aznar Benitah, Ph.D., ICREA researcher at IRB Barcelona.

The team used sophisticated population- and single-cell transcriptomic techniques, together with lineage tracing, to investigate whether mouse dermal fibroblasts change during the normal course of physiological aging, and under different dietary regimes. Their findings suggested that the identity of old fibroblasts essentially becomes less defined, or blurred. The dermal fibroblasts also demonstrated reduced expression of genes involved in forming the ECM, and instead took on adipogenic traits, “paradoxically becoming more similar to neonatal pro-adipogenic fibroblasts,” they write. “Besides the acquisition of identity noise, we show that old fibroblasts lose production and secretion of ECM components yet concomitantly upregulate the expression of genes involved in inflammation, lipid metabolism, and adipogenesis.”

Interestingly, while old dermal fibroblasts from mice on a CR diet were still distinguishable from young dermal fibroblasts, they didn’t display the same level of changes in transcription as old fibroblasts from animals on normal diets. The CR diet appeared to delay the consequences of aging on the cells. Some of these age-defying effects were maintained for months even after the animal were put back on a normal diet, while others required caloric restriction to continue. “This suggests the interesting hypothesis that some aspects of the rejuvenating potential of caloric restriction are stable, while others require a constant CR diet,” they write. In contrast, the transcriptional signatures of fibroblasts taken from adults fed a high-fat diet were similar to those of old fibroblasts.

“The notion that the loss of cell identity is one of the underlying causes of aging is interesting and one that we believe hasn’t been considered before,” Dr. Aznar Benitah commented. Acknowledging that the studies to date represent basic research, he concluded, “… this new knowledge might not only have cosmetic applications, for example, anti-aging skin treatment, but more importantly, also therapeutic applications aiming to help aged skin to form scar tissue faster and more efficiently after being damaged or after an operation”.

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