Mikolaj Ogrodnik

Background: Skin aging is a complex process, marked by structural decline, functional impairment, and diminished regenerative capacity. In this study, we shine a spotlight on the transcription factor Foxn1 and its pivotal role in modulating age-related changes in skin architecture and redox homeostasis. Using a murine model across three life stages (young — 20-days-old, middle-age — 1-year-old, old — 2-year-old), we compared wild-type (Foxn1 ^+/+ ) and Foxn1 heterozygotic knock out (Foxn1 ^+/− ) mice to unravel the interplay between genetic regulation and skin aging. Results: Our findings reveal a striking impact of Foxn1 on skin morphology: Foxn1 ^+/− mice displayed thinner epidermis, thicker dermis, and disrupted keratinocyte differentiation, favoring large spinous layer of epidermal cells. Notably, the skin of Foxn1 ^+/+ mice was associated with increased collagen I and a shift toward repair-oriented fibers, whereas Foxn1 ^+/− skin maintained elevated collagen III, hinting at a preserved regenerative profile. Additionally, while p21 expression rose with age in Foxn1 ^+/+ mice, it remained low in Foxn1 ^+/− mice, suggesting an altered senescence pathway. Intriguingly, Foxn1 also emerged as a modulator of the hypoxia response, oxidative stress levels, and cellular protection, particularly in young and middle-age mice. These effects diminished with advanced age, underscoring Foxn1’s age-dependent regulatory dynamics. Conclusions: Together, these results position Foxn1 as one of key regulators of skin homeostasis and reveal its potential role in skin aging processes.

Cellular senescence plays key roles in tissue repair, tumour suppression and ageing. Here we identify a rapid, transcription‑independent senescence response in skin following injury. Within minutes to hours after wounding, skin cells at the edge of injury display hallmark features of senescence. This response involves the utilization of pre‑existing Cdkn1a mRNA through the removal of nuclear export inhibitors, which enables Cdkn1a transcript translation and rapid p21 protein accumulation. These cells enter stable cell‑cycle arrest and secrete pro‑migratory and pro‑inflammatory factors that promote tissue repair, including re‑epithelialization. Experimental suppression of this rapid senescence, either genetically or pharmacologically, markedly delays wound closure, whereas inhibition during later phases of repair has no effect. Our findings establish rapid‑onset senescence as a mechanistic requirement for efficient tissue regeneration.

Migraine may signal early signs of aging-related processes, such as reduced autophagy, increased reactive oxygen and nitrogen species (RONS), and low-grade

Aging is a complex biological process leading to functional decline and disease susceptibility. This article proposes that chronic activation of tissue damage response mechanisms drives aging, with aged organs exhibiting features similar to those seen after acute injury, such as histolysis, inflammation, immune cell infiltration, accumulation of lipid droplets, and induction of cellular senescence. The overlap between injury and aging phenotypes is supported by evidence that interventions slowing aging often impair healing, and vice versa. This perspective offers a unifying framework to understand aging and suggests new directions for treating age-related diseases, cancer, and the aging process.

Biological processes are often spatially regulated, ensuring molecular and cellular events occur in their most strategically advantageous locations. Cellular senescence, marked by cell cycle arrest and hypersecretion, is recognized as an important part of physiological processes like development and healing, but it also contributes to aging and disease. However, the spatial distribution of senescent cells and its physiological and pathological impact remain unclear. Here we compile evidence on senescent cell localization in development, healing, and aging. We emphasize the significance of their spatial patterns and speculate on the effects of disrupted spatial positioning of senescence in relation to pathologies. To summarize the specific spatial functions of senescent cells, we propose to refer to them as ‘barrier’ and ‘conductor’ functions. The ‘barrier’ function of senescent cells, due to their altered morphology and apoptosis resistance, separates tissues and builds a border between two environments. The conductor function, with the secretion of signaling factors, influences the surrounding area and stimulates migration, differentiation, or proliferation, among other processes. Overall, this Review explores the spatial patterning of cellular senescence in biological processes, highlighting its dual roles as ‘barrier’ and ‘conductor’ functions, and examines the implications of senescent cell distribution in development, healing, aging, and disease.

With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, epigenetic aging and stem cell alterations. We draw a distinction between the causes and consequences of aging and define short-term consequences as ‘responses’ and long-term ones as ‘adaptations’. We also discuss ‘damaging adaptations’, which despite having beneficial effects in the short term, lead to exacerbation of the initial insult and acceleration of aging. Features commonly recognized as ‘basic mechanisms of the aging process’ are critically examined for the possibility of their adaptation-driven emergence from processes such as cell competition and the wound-like features of the aging body. Finally, we speculate on the meaning of these interactions for the aging process and their relevance for the development of antiaging interventions.