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Researchers Claim Serum Albumin Increases Mouse Lifespan

They report they have increased mouse lifespan by 20%.

AlbuminAlbumin
 

Before we begin, it should be noted that this study was published on biorxiv, a pre-print website that hosts papers prior to peer review. Therefore the data should not be regarded as conclusive or accurate until it has been subject to the peer review process and accepted for journal publication. Please keep that in mind while reading this article and also when assessing the pre-print itself.

Researchers behind a new manuscript claim that the lifespans of middle-aged mice can be increased up to 20% with a treatment of recombinant serum albumin every 3 weeks.

Serum albumin is a component of blood plasma in vertebrates, produced by the liver, and the most common blood protein found in mammals. Albumin maintains the oncotic pressure needed for the correct distribution of fluids between blood vessels and bodily tissues. Without the presence of albumin, the high pressure of the blood vessels would push more fluids into the tissues. Additionally, serum albumin is a plasma carrier, as it binds several hydrophobic steroid hormones, and it acts as a transport protein for hemin and fatty acids.

The study builds on the existing work of researchers such as Drs. Irina and Michael Conboy, who have demonstrated that aging includes modification of circulating blood factors, including serum albumin. Most recently, they showed that diluting aged blood rejuvenates old brains, improving cognition, reducing neuroinflammation, and spurring neurogenesis in old mice.

Researchers report increased longevity with albumin treatment

The researchers of this study hypothesized that at least some of the detrimental effects of aging are due to changes to serum albumin and the harmful reactions to it [1]. This makes total sense given that the bloodstream is essentially the internet of the body, allowing distant parts to communicate with each other and to react to the signaling factors circulating in the blood.

They proposed to test this by delivering unmodified serum albumin to middle-aged mice in order to dilute the presence of damaged albumin in the animals. In essence, their aim was to intervene against this aspect of aging by reversing the damaging responses to pro-aging signals in the blood.

It was unknown if this process might increase lifespan; as while previous experiments had consistently shown that rejuvenation of tissue and organs was possible, no lifespan studies had ever been carried out before, most likely due to the high costs of such studies.

The middle-aged mice (12 months old) were given serum albumin at 1.5 mg per gram of body weight or isometric saline every 3 weeks for the control group until the animals died naturally. A lifespan increase of 17.6% for females and 20.3% for males was reported by the researchers at the end of the study. The researchers also claimed that the appearance of animals of both sexes were better in the treated group, with glossier and thicker fur apparently being observed.

In addition to increased longevity, the researchers claimed that the treated mice also had increased grip strength and were better able to escape from a Barnes maze test.

Improvement of longevity is an eternal dream of human beings. 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, UniProtKB P02768) 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 Pro, Arg, Lys and Thr 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.

Conclusion

There has been considerable debate recently about whether experiments like this work by restoring lost beneficial factors in aged blood or by reducing harmful factors. If the study results here are to be believed, then it suggests that fresh albumin is enough to increase lifespan in mice. It may be the case that introducing fresh albumin to aged blood dilutes the pro-aging factors and perhaps even compensates for the existing potentially damaged albumin already present. However, more research is needed in order to establish this and the study should ideally be replicated independently,

In general, we are enthusiastic about interventions that seek to dilute, block, or even remove the harmful signals present in aged blood. We believe that they may potentially be the first true rejuvenation therapies to reach humans, given that the technology to do this is already available with little modification and would be relatively inexpensive to implement at scale.

If you are interested in learning why we have such optimism, take a look at last year’s interview with the Conboys. In fact, one group of biohackers in Russia was so excited about the idea that they couldn’t wait and decided to conduct their own longevity experiment on themselves. You can learn more about their biohacking experiment here.

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Literature

[1] Tang, J., Ju, A., Li, B., Zhang, S., Gong, Y., Ma, B., … & Luo, Y. (2021). Young and Undamaged rMSA Improves the Longevity of Mice. bioRxiv.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. Dean Robinson
    April 9, 2021

    Nigella Sativa increases serum albumin levels to some degree. Would increasing hsa levels have a similar effect as these latest studies?

  2. Adrian Cull
    April 11, 2021

    Unfortunately, there was no increase in maximum lifespan. That is the measure I’m particularly interested in on the path to robust mouse rejuvenation which will need to see mice live to 5 years old.

  3. Neil
    April 11, 2021

    The plot thickens…

    I absolutely love how quickly our understanding of rejuvenation of the blood is moving and how much “bang” we can achieve with so little “buck”. To follow up, I hope the Conboys perform a dilution experiment with multiple groups, amongst which would be diluted blood with old replacement serum, diluted blood with young replacement serum and another group with diluted blood and rMSA. That should help clarify how much of the effect comes from dilution and how much comes from introduction of youthful albumin.

    On the point Adrian made about maximum lifespan, it doesn’t completely surprise me. There are multiple things that need to be fixed and this doesn’t fix all of them. It is nevertheless extremely exciting because of how impactful, easy, non-invasive and inexpensive it is and that it is essentially already FDA approved.

    Great article Steve!

  4. April 14, 2021

    I am curious by nature and I don’t know if I am on the right track here. Doesn’t extending lifespan requires telomere extension? Also if development is fairly uniform in all human bodies, there needs to be a reliable regulator of aging in our cells.
    If healthy lifespan of mice can be increased without increasing maximum lifespan, then it may mean that reverting the body back to a healthier state is not everything. It would very well mean that the aging happens in a faster pace later in life. Telomere length is not a good measure of aging. But aging may depend on telomere signaling: https://www.nature.com/articles/nrg3743

    So I leave this comment here, because as I read more and more about aging research, the more I am convinced about the role of telomeric region in epigenetic alterations. And I would welcome any opinions.

  5. mpease
    May 8, 2021

    Unfortunately no mouse is going to be able to afford this stuff @ up to 2500 a bottle. Maybe that ratatouille mouse could.

    https://www.albuminbio.com/our-shop/recombinant-mouse-albumin/recombinant-mouse-serum-albumin/

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