Human Serum Albumin is the most abundant protein in the plasma. It now appears that human serum albumin produced in a recombinant bacterial expression systems, [7,8] can deliver pharmacological levels of “young,’ undamaged, reduced or un-oxidized [9] and appropriately folded recombinant Human Serum Albumin (rHSA). When this rHSA is administered to a mammal it results in profound age regressive benefits that include increases in physical strength, mental capacity and increased longevity. These rHSA proteins are devoid of, or incorporate dramatically reduced amounts of age associated, accumulated / unnecessary modifications. These can include; free thiols, carbonation, glycation end-products or homocysteinylation. The resulting recombinant biologically active protein becomes a dramatic age regressive intervention. The expression of these proteins in yeast cultures provides for a relatively inexpensive and limitless supply of these proteins. [10] These humans proteins can also be expressed in plants and lower mammalian species.

▶︎ 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. ◀︎[6]

▶︎ Serum free thiols and protein thiols are converted to disulfides with aging [83]. Specifically, Era et al. reported the comparison of serum ALB redox state in young and old subjects (18–24 vs. 60–90 years of age) using HPLC as early as in 1995 [17]. It was found that HMA ratio was obviously higher in the old subjects compared with young subjects. Oettl et al. also presented in their review article that both HNA-1 and HNA-2 ratio increased with aging (ranging approx. 10–100 years of age) [10]. Similarly, Rossi et al. reported increases in cysteinylation and homocysteinylation of plasma proteins with aging in healthy subjects aged 20–93 [84]. Increases in HNA ratios with aging have been further confirmed in recent studies on patients and healthy controls [32,77]. The rationale for these observations has been attributed to oxidative stress accelerated by aging.◀︎[2]

In 2014, Wyss-Coray group reported that plasma from young mice can improve the learning and memory of old mice. Since albumin occupies about 50% of total plasma proteins, it most likely plays the most important role in this process, which was exactly what we found here. In order to achieve the maximal effect of rMSA on longevity, a variety of measures including optimal dosage, frequency, and drug delivery methods are being investigated. We predict that the concept of young and undamaged albumin increasing the longevity can also be applied to any other proteins such as immunoglobulins, fibrinogen, transferrin, transthyretin, and haptoglobin which are major plasma proteins. If so, the combination of young and undamaged major plasma proteins can further increase the longevity. Ideally, all of the young and undamaged plasma proteins altogether can increase the longevity to the largest extent.[6]