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Senescent cell transplantation into the skin induces age‐related peripheral dysfunction and cognitive decline

机译:衰老细胞移植到皮肤中会诱发与年龄相关的外周功能障碍和认知能力下降

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摘要

Cellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age‐associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence‐associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.
机译:细胞衰老是细胞和组织衰老的既定原因。衰老细胞已被证明在衰老过程中多个器官(包括皮肤)中增加。在这里,我们假设居住在皮肤中的衰老细胞可以将衰老传播到远处的器官,从而加速全身衰老过程。为了探索这一假设,我们最初观察到老年小鼠皮肤中几种衰老标志物的增加。随后,我们进行了实验,将衰老的成纤维细胞移植到年轻小鼠的真皮中,并评估了各种与年龄相关的参数。我们的研究结果表明,年轻小鼠真皮层中存在衰老细胞会导致近端和远端宿主组织的衰老增加,同时虚弱增加,肌肉骨骼功能受损。此外,认知功能显着下降,伴随着海马脑区衰老相关标志物的表达增加。这些结果支持这样一个概念,即衰老细胞在皮肤中的积累可以对包括大脑在内的其他器官产生远程影响,可能解释皮肤与大脑疾病之间的联系,并导致与衰老相关的身体和认知能力下降。

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