engleski

Modulation of skin homeostasis and regeneration - a novel aproach

In Europe and in Croatia the percentage of elderly persons has sharply risen and represents a signficant socio-economic problem which weighs heavily on the financial and health prospects of society. Aging is the main risk factor in the emergence of pathological conditions and tumor incidence. The aging phenotype develops as a result of the reduced potential for tissue regeneration concomitant with the destruction of tissue homeostasis and the accumulation of damaged molecules. Cellular senescence, a process in which cells reach their maximal limit of doublings, is the main catalyst of aging of humans. Old cells have a characteristic gene expression profile, highlighted by a strong increase in secreted cytokines, chemokines, proteinases and growth factors. This secretory phenotype is known as SASP (senescence-associate secretory phenotype) and includes a variety of inflammatory and growth factors which act to remodel the tissue microenvironment, activate the cellular immune response and elicit an inflammatory metabolic profile, all of which has a negative impact on stem cells and regeneration. Expression of the enzyme telomerase prevents aging and allows for the continuous expression of the young phenotype. The model in which the accumulation of old cells directly elicits pathophysiological changes could be tested by directly altering the proportions of old versus young cells in tissues. This can be achieved by increasing the number of young cells or telomerase revitalized cells through microseeding in skin tissue. In this way we expect to increase the regenerative capacity of cells, reconstruct the youthful tissue microenvironment and extracellular matrix of the skin. To this end we have established a protocol for microseeding of cells in skin tissue which allows for alterations in the number of old vs. young cell populations. The main objective of this research is to directly show that it is possible to alter the cellular composition of tissues and show that by decreasing the number of old cells and increasing the number of young cells in a tissue one can alter the local tissue metabolic profile to activate regeneration.

aging ; skin ; regeneration ; stem cells ; homeostasis

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