An interesting result is reported in today's open access preprint paper. The authors find that the life span of mice is extended by 20% or so after treatment every few weeks with serum albumin, beginning in mid-life. The researchers base their approach on noting that aging is characterized by modification of circulating serum albumin molecules, and theorize that a significant fraction of the issues arising with age are reactions to that damaged albumin. By delivering unmodified serum albumin, the damaged fraction of albumin is reduced, and the harmful reactions diminish. This is, in effect, sabotaging one of the many feedback loops in aging wherein forms of molecular damage act as signals to provoke maladaptive responses and further molecular damage.
This is most interesting when considered in the context of the beneficial effects that are reported to result from dilution of blood in old animals. Dilution studies have been carried out as a part of the ongoing debate over whether contributions to aging result from a loss of beneficial factors in circulating blood, or from the addition of harmful factors to circulating blood. That this dilution is enough to produce some degree of reversal of aspects of aging, such as chronic inflammation, argues for the harmful factor model. It is important to note that the dilution protocol involves adding albumin, as albumin is one of the few essential items present in the bloodstream that will result in major issues should it fall to lower levels. Is the added compensatory albumin the primary cause of benefits? Further studies will be needed to clarify and replicate these results.
Here we report that a single protein recombinant mouse serum albumin (rMSA) improved the lifespan and healthspan of C57BL/6N mice. The median lifespan extensions were 17.6% for female and 20.3% for male, respectively. 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. 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 advanced glycation end-product, no carbonylation, and no homocysteinylation. Here "young and undamaged" rMSA is much younger and less damaged than the endogenous serum albumin from young mice at 1.5 months of age. We predict that young and undamaged proteins altogether can further improve the longevity.
Human serum albumin (HSA) is the most abundant protein in blood plasma with a serum half-life of about 21 days. Damages or unnecessary modifications of HSA are related to many pathological conditions and increase with age. Firstly, the single free thiol in Cys-34 residue of HSA has been proposed to account for approximately 80% of the total free thiols in plasma, whose oxidation is intimately linked with aging and age-related diseases. Secondly, in oxidative environments, carbonyls are also formed especially on the side chains of residues in proteins. Elevated carbonyl levels in HSA have been found to be related to aging and varieties of diseases. Thirdly, the AGE accumulation of HSA is another important factor found to be involved in aging. It is widely reported that AGE formation impairs normal functions of albumin and can induce inflammatory responses, which is connected with aging and the progression of serious diseases. Fourthly, it has been widely reported that homocysteine (Hcy) increases with age and is associated with age-related degenerative disorders. HSA is a major target for homocysteinylation, thus it can efficiently protect other proteins from the toxicity of Hcy.
Therefore, treatment of freshly prepared recombinant serum albumin with no damages or unnecessary modifications is most likely to extend lifespan and healthspan. Here we report that young and undamaged recombinant mouse serum albumin (rMSA)-treated groups in natural aging mouse model obtained significantly extended lifespan with increased skeletal muscle strength and cognitive ability compared with saline-treated groups.