Aging, though a natural process can come with a feeling of dread for many. It is no wonder that for a long time now humans have sought ways to stop or delay the process, and although we have not been completely successful, we try nonetheless. Most of these efforts to delay the aging process are focused on preventing age-related skin changes like skin wrinkles and dryness.
In a recent publication in Aging Volume 14, Issue 9, a single-cell transcriptomics study uncovered the reason for age-resistant maintenance of cell identities, stem cell compartments, and differentiation trajectories in old naked mole-rats skin. The study aims to apply the result in inhibiting the aging process in humans both for cosmetic and health purposes.
Role of the skin in the aging process
The protective function of the skin plays a pivotal role in the aging process. It protects humans and animals from external risks, prevents fluid loss, stabilizes body temperature, and houses receptors and nerves that relay information to the brain. The maintenance of the normal functioning of the skin is essential, as skin dysfunctions can result in deleterious conditions ranging from fluid loss to more severe diseases like infections or UV-induced carcinomas, associated with aging. It is no wonder then that most anti-aging therapies are usually targeted toward maintaining skin functions.
Unraveling age resistance in naked mole rats (NMR)
NMRs are underground rodents known for having remarkable longevity and unique resistance to the aging process. Unlike other species, NMRs exhibit striking stability of skin compartments and cell types that maintained stability over time without the usual age-associated changes.
The research team hypothesized that the observed maintenance of cellular compartments in older NMR, especially the stem cell pools that occur through Igfbp3 expression, and the increased skin immunity could explain the slower skin aging process.
Using single-cell RNA sequencing to obtain an objective molecular RNA profile of the naked mole rats’ epidermal cell populations, the researchers discovered an unchanged epidermal gene expression despite aging. In fact, the three classical cellular states that defined a unique keratinocyte differentiation were not also unaltered after pseudo-temporal reconstruction.
They also found similarities between the skin healing closure between the younger and older NMR. Interestingly, the number of stem cells also remained unchanged throughout aging. On analysis, the NMR epidermal cells revealed two main populations, immune cells, and keratinocytes arranged in one and ten clusters respectively. Further analysis revealed that in each cluster, they discovered an overexpression of 2 genes in the basal stem cells and 5 genes in the immune cells of older animals.
They postulated that the NMR skin showed peculiar genetic and cellular features and these features and that the observed stability of the aging NMR skin transcriptome likely explains the age resistance.
The results of the study could be used in the prevention of age-associated skin dysfunction which in turn could help prevent skin diseases associated with the aging process.
This study fits a piece into the existing puzzle of the aging process and provides a foundation for new discoveries and insight into preventing age-related changes associated with skin dysfunction.