ILANIT 2023

Stimulation of wound healing by potential longevity-promoting interventions

Anna Knyazer 1 Denis Tolstun 2 Khachik Muradian 2 Yael Segev 1 Marina Wolfson 1 Vadim Fraifeld 1,2
1The Shraga Segal Department of Microbiology, Immunology and Genetics, Center for Multidisciplinary Research on Aging, Ben-Gurion University of the Negev, Beer Sheva, Israel, Israel
2State Institute of Gerontology of National Academy of Medical Sciences of Ukraine, Kiev, Ukraine

We have recently shown that a chronic exposure of mice to self-produced hypoxic/hypercapnic environment (HHE) could induce metabolic remodeling, resulting in a long-term and substantial decrease in metabolic rate, body temperature, and food consumption—conditions that are strongly associated with life span extension. However, the hypometabolic state may affect the basic biological processes, such as tissue wound healing (WH). With this in mind, we evaluated the impact of chronic HHE on the rate of skin WH in C57Bl/6 mice. Surprisingly, despite the lower energy expenditure, HHE significantly accelerated the closure of head excisional wounds. This could in part be attributed to enhanced mobilization and functional capacity of mesenchymal stem cells in response to HHE. An increase in the pool of stem cells could be another life span-extending intervention. Using in vitro model of WH, we further showed that the cocktails of selected small molecules (SM) for cell reprogramming (i) significantly increased the Side Population stem cells in primary cultures of human fibroblasts, and (ii) accelerated the closure of the cell gap.