Abstract
The blood exhibits a dynamic flux of proteins that are secreted by the tissues and cells of the body. To identify novel aging-related circulating proteins, we compared the plasma proteomic profiles of young and old mice using tandem mass spectrometry. The expression of 134 proteins differed between young and old mice. We selected seven proteins that were expressed at higher levels in young mice, and confirmed their plasma expression in immunoassays. The plasma levels of anthrax toxin receptor 2 (ANTXR2), cadherin-13 (CDH-13), scavenger receptor cysteine-rich type 1 protein M130 (CD163), cartilage oligomeric matrix protein (COMP), Dickkopf-related protein 3 (DKK3), periostin, and secretogranin-1 were all confirmed to decrease with age. We then investigated whether any of the secreted proteins influenced bone metabolism and found that CDH-13 inhibited osteoclast differentiation. CDH 13 treatment suppressed the receptor activator of NF-κB ligand (RANKL) signaling pathway in bone marrow-derived macrophages, and intraperitoneal administration of CDH-13 delayed age-related bone loss in the femurs of aged mice. These findings suggest that low plasma CDH-13 expression in aged mice promotes aging-associated osteopenia by facilitating excessive osteoclast formation. Thus, CDH-13 could have therapeutic potential as a protein drug for the prevention of osteopenia.
Highlights
Aging is a time-dependent functional decline that is characterized by the progressive loss of physiological integrity, leading to organ dysfunction and increased vulnerability to age-related diseases [1]
Plasma proteins that change with aging have been documented in many ways, few studies have systematically explored and characterized the proteins that influence the aging process and agerelated diseases
When we compared our listed proteins with those identified by the 2D-DIGE and SOMAscan approaches, we found little overlap
Summary
Aging is a time-dependent functional decline that is characterized by the progressive loss of physiological integrity, leading to organ dysfunction and increased vulnerability to age-related diseases [1]. Since plasma proteins reflect human physiological or pathological states, they are a potential goldmine of candidate biomarkers for age-related changes [5]. The study of such markers could clarify the physiological processes of aging, which in turn could provide insights into potential therapeutic targets and strategies to alleviate the effects of aging [6, 7]. The injection of aged mice with recombinant apelin was reported to reverse age-related losses of muscle mass and strength [16]. These findings suggest that specific factors in young or old plasma can contribute to the aging process and/or age-related diseases
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