Fight Aging!

Cells become senescent at some pace throughout the body and throughout life, largely by reaching the Hayflick limit on replication, but also under other circumstances, such as when a cell sustains potentially cancerous mutational damage. A senescent cell ceases replication and actively secretes pro-inflammatory signals that (a) encourage senescence in bystander cells and (b) attract the attention of the immune system to destroy the senescent cell. This is all find so long as the immune system can destroy senescent cells rapidly enough to prevent their accumulation, but this stops being the case in later life as the immune system declines in effectiveness. Senescent cells accumulate and become disruptive to tissue structure and function.

Researchers have in the past shown that introducing senescent cells into joint tissue in mice is enough to induce or accelerate osteoarthritis. In today's open access paper, researchers report on the introduction of senescent cells into the skin of 3 month old mice, followed by assessment of a range of measures of health 5 months later. Mouse age doesn't linearly relate to human age, but this is roughly equivalent to the range of early 20s to early 40s in humans. One would not expect to see dramatic signs of aging in 8 month old mice, but there are measurable differences, declines in function. This study demonstrates that the presence of a greater burden of senescent cells makes those declines worse.

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

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.

A limitation of our study is that the amount and composition of transplanted senescent cells does not accurately reflect senescent cell accumulation during physiological aging. Future research should include other models of senescence induction in the skin, including exposure to physiological levels of UV irradiation. Furthermore, to determine whether paracrine senescence is the causal factor driving the observed aging phenotypes, experiments involving the clearance of senescent cells using senolytic drugs or genetic models that enable the removal of p16 or p21 positive cells should be conducted. In addition, further research is needed to pinpoint which factors released by senescent cells in the skin drive the systemic effects observed in host tissues. Such mechanistic studies could open new avenues for therapeutic intervention.