Mice lacking a signalling protein called MKP-2 showed fewer signs of premature cell ageing, better insulin sensitivity and healthier fat metabolism, and they lived longer. The finding is early and comes from animals, but it points to fat tissue as a place where ageing can be influenced.
A research team has reported in the journal Aging Cell that removing a single protein, mitogen-activated protein kinase phosphatase-2 (MKP-2), protects mice from the premature ageing of cells and fat tissue, improves their metabolic health and extends their lifespan. MKP-2 belongs to a family of enzymes that switch off cellular signalling pathways responding to growth factors, stress and nutrients.
Cells that stop dividing
The work centres on cellular senescence, a state in which a cell permanently stops dividing but does not die. Senescent cells accumulate with age and in obesity, and they release inflammatory molecules, collectively called the senescence-associated secretory phenotype, that can damage neighbouring tissue.
In cultured mouse embryonic fibroblasts, cells lacking MKP-2 showed markedly less senescence-associated β-galactosidase activity, the standard staining marker, than normal cells. When the researchers put MKP-2 back through gene transfection, the premature senescence returned, which suggests the protein itself drives the effect.
Younger-looking fat in old mice
The effect also appeared in living animals. In 19-month-old mice fed a high-fat diet, the MKP-2-deficient animals had lower β-galactosidase activity and lower levels of the senescence markers p16 and PAI-1 in the white fat around the epididymis. Their fat cells also kept more lamin B1, a structural protein whose loss is linked to senescence, showed less phosphorylation of the stress protein p53, and produced lower levels of inflammatory signals such as IL-6 and CCL2.
According to the authors, the loss of MKP-2 also changed the lipid composition of fat tissue, improved insulin sensitivity and fat metabolism, and extended the animals’ lifespan.
How the finding fits earlier work
The result is consistent with earlier hints. A 2003 study of human fibroblasts found that MKP-2 was more abundant in senescent cells than in young ones, because the protein degraded more slowly. A 2023 master’s thesis at the University of Alabama in Huntsville reported that fibroblasts from MKP-2 knockout mice were resistant to senescence. The new paper extends that cell-culture finding to whole animals and to lifespan.
What the study does not show
This is a mouse study in which the gene was deleted, which is very different from a drug. Removing a gene from birth is not the same as partially blocking a protein later in life, and the long-term effects of losing MKP-2 throughout the body are not established. The key tissue results come from animals fed a high-fat diet, so it is not clear how far they apply to lean or healthy animals. Lifespan extensions in mice also often fail to carry over to people, so the finding is best read as a lead on a biological mechanism, not a treatment.
Why the region should care
Fat-tissue ageing and insulin resistance are central to type 2 diabetes, which is a heavy burden in Central and Eastern Europe. A recent modelling study from the University of Debrecen puts diabetes prevalence at about 7 per cent of adults in the CEE countries it covers, notes that rates are higher there than in much of Europe, and points to higher physical inactivity among adults in the region.
For countries with ageing populations and high rates of obesity and diabetes, research that links cellular ageing to metabolic disease is directly relevant, even when the first results come from mice. Any practical benefit for patients would be many years away, and the proven measures against metabolic disease in the region remain diet, activity and early treatment of diabetes.
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