Osteopontin Plays Diverse Roles in Degenerative Aging

Osteopontin levels are higher in blood samples taken from older people than in those taken from young people. It is a component of the senescence-associated secretory phenotype (SASP) produced by senescent cells, disruptive to tissue function. Osteopontin acts as a regulator in a number of tissues, and appears to be relevant to the age-related decline, such as of hematopoiesis and muscle function. Here, researchers review what is known of the role of osteopontin in aging.

Osteopontin (OPN) is a multifunctional noncollagenous matrix phosphoprotein that is expressed both intracellularly and extracellularly in various tissues. As a growth regulatory protein and proinflammatory immunochemokine, OPN is involved in the pathological processes of many diseases. Recent studies have found that OPN is widely involved in the aging processes of multiple organs and tissues, such as T-cell senescence, atherosclerosis, skeletal muscle regeneration, osteoporosis, neurodegenerative changes, hematopoietic stem cell reconstruction, and retinal aging. However, the regulatory roles and mechanisms of OPN in the aging process of different tissues are not uniform, and OPN even has diverse roles in different developmental stages of the same tissue, generating uncertainty for the future study and utilization of OPN.

Numerous research results have shown the dual roles of OPN in the aging process. For example, in the nervous system, OPN not only causes neurotoxicity but also acts as a neuroprotective agent for Parkinson's disease. In the process of liver aging, OPN not only induces the occurrence and development of age-related liver fibrosis but also delays the aging and apoptosis of hepatocytes and promotes their regeneration by restoring the autophagy activity of aging liver cells. In addition, OPN also plays a dual role in the process of eye aging. On the one hand, in the early stage of the disease, OPN expression increases to mediate its protective effect on adverse pathological changes. On the other hand, excessive accumulation of OPN aggravates calcification and calcium deposition in tissues, which is an important link in pathological degeneration.

The role of OPN in the aging process has not been fully clarified. More importantly, the critical point of this phenomenon is not completely clear. Therefore, further in-depth studies investigating whether OPN mediates and participates in the effects of antiaging factors such as sports, nutrition, and healthy lifestyle on the aging process are worthwhile and will hopefully provide new ideas and treatment schemes for many clinical diseases in the future.

Link: https://doi.org/10.3389/fendo.2022.1014853