Abstract

Improvement of longevity is an eternal dream of human beings. The accumulation of protein damages is considered as a major cause of aging. Here, we report that the injection of exogenous recombinant mouse serum albumin (rMSA) reduced the total damages of serum albumin in C57BL/6N mice, with higher level of free-thiols, lower levels of carbonyls and advanced glycation end-products as well as homocysteines in rMSA-treated mice. The healthspan and lifespan of C57BL/6N mice were significantly improved by rMSA. The grip strength of rMSA-treated female and male mice increased by 29.6% and 17.4%, respectively. Meanwhile, the percentage of successful escape increased 23.0% in rMSA-treated male mice using the Barnes Maze test. Moreover, the median lifespan extensions were 17.6% for female and 20.3% for male, respectively. The rMSA used in this study is young and almost undamaged. We define the concept “young and undamaged” to any protein without any unnecessary modifications by four parameters: intact free thiol (if any), no carbonylation, no advanced glycation end-product, and no homocysteinylation. Here, “young and undamaged” exogenous rMSA used in the present study is much younger and less damaged than the endogenous serum albumin purified from young mice at 1.5 months of age. We predict that undamaged proteins altogether can further improve the healthspan and lifespan of mice.

Highlights

  • Longevity is an eternal pursuit of human beings

  • Exogenous recombinant mouse serum albumin (rMSA) Treatment Reduced the Damages of Endogenous Albumin

  • We proposed for the first time that the status of free thiol, carbonyl, advanced glycation end-product (AGE), and hcy can define a young and undamaged protein

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Summary

Introduction

Longevity is an eternal pursuit of human beings. Tales of passionate seeking for immortality run through the whole human history. Egerman group and Villeda group, respectively, found that the muscle strength and cognitive ability of old mice were improved after the parabiosis surgery with young mice [2,3], which suggest that the “mystery” of aging may exist in blood proteins. It is believed that aging is at least partially caused by the continuous accumulation of damages or unnecessary modifications of proteins [4,5,6], including free thiol oxidation, carbonylation, advanced glycation end-product (AGE) formation, and homocysteinylation [7,8,9,10]. Human serum albumin (HSA, UniProtKB P02768) is the most abundant protein in blood plasma with a serum half-life of about 21 days [11]. Damages or unnecessary modifications of HSA are related to many pathological conditions and increase with age

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