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Can Rats Reverse Aging?

Naked mole rats live long lives, maintaining youthful bodies by regularly clearing away senescent cells from their bodies. Scientists are now investigating ways of mimicking this process in order to stay youthful themselves.

Pig blood plasma was used to turn back time for liver, blood, heart tissue and the hypothalamus in rats.

They Reverse the Biological Clock

We developed six DNA methylation-based age estimators (“clocks,” in machine learning terminology) on 503 rats from four labs using different tissues or measures of aging (blood, brain, liver and pan-tissue clocks). Two additional clocks that apply both to rats and humans were trained using data combining 503 human tissue samples with the training set used by rat clocks.

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Rat clocks provided unbiased estimates of age with strong correlations to chronological age across many tissue types; some were more sensitive than others. For instance, brain and blood clocks had higher correlations to chronological age than pan-tissue clocks – this can be explained by different biological mechanisms for aging which vary between tissues – as their methylation profiles reflect this variability.

Plasma fraction treatment dramatically decreased the sensitivity of rat clocks, leading to significant decreases in age estimation errors and significantly lowering age estimate errors. This finding supports other evidence suggesting that plasma fraction reverses biological aging processes by modulating oxidative stress levels and cell autophagy processes.

Oxidative stress is an inevitable part of cell function, but at high levels it can compromise biomolecules and interfere with their functionality. One way of measuring the amount of oxidative stress in cells is measuring malondialdehyde (MDA), an end product of polyunsaturated fatty acid peroxidation. For rats aged 24-30 months untreated with plasma fraction treatment had higher MDA levels in the brain, heart, and liver than younger animals while treating with plasma fraction brought them down to levels comparable to younger rats’ levels.

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An experiment comparing the ability of old and young rats to complete a Barnes maze task revealed that older untreated rats had longer latency periods compared to younger untreated rats, but after one month of plasma fraction treatment their latency periods became significantly shorter than untreated ones due to reversed brain ageing and restoration of youthful autophagy levels.

They Rejuvenate the Brain

Researchers used light to strengthen memory cell connections in rats. Scientists provided low-frequency pulses of light to the rodents’ skulls, making their nerve bundles respond as if being shocked; this led the rodents to recall having experienced this pain before and associating it with fear; once stimulated with high-frequency pulses again, these rats would freeze up with fear even though their feet weren’t being touched; Malinow and his colleagues successfully “restored” this fear-linked memory linkage which had previously existed!

Researchers conducted two separate studies that have restored neural circuits used by rats and mice for scent detection, using proteins that sense brain stiffness to keep these circuits functioning despite how stiff their bodies have become over time.

Studies have also demonstrated the benefits of administering young blood plasma to older animals in order to help their organs and tissues function more optimally. A preliminary research paper conducted using plasma fraction treatment from young pig blood showed dramatic reductions in epigenetic age across various organs and tissues from rats; blood, liver, heart, hypothalamus – including brain tissue where treatment more than halved the epigenetic age!

Scientists gave this treatment to older rats and found they outperformed untreated rats in various learning and memory tests, including escape from water mazes designed to test spatial reference memory. Furthermore, treated old rats escaped faster from mazes than their untreated counterparts. Although these findings are intriguing, it’s unlikely to apply directly to humans as the markers of aging seen in rats can differ substantially across mammalian species.

They Reverse the Age of the Heart

Scientists claim they have taken one step towards reversing aging after rejuvenating worn-out organs in elderly mice at the Salk Institute. Their treatment partially reset cells back to more youthful states while simultaneously improving animal health and performance. Researchers used Yamanaka factors derived from young pig plasma fractions as part of this initiative and published results showing more than half an age decrease for blood, liver and heart tissues – as reported in Nature Aging’s results from this research study.

This marks the first time that cross-species therapy has successfully reversed cellular aging. Rats experienced biological age reversal thanks to young pig plasma’s extracellular nanoparticles (exosomes). Exosomes are small vesicles containing bioactive molecules and act as messengers between cells. By injecting pig plasma into older rats, researchers were able to deliver exosomes containing these rejuvenating factors directly into their cells – leading to unparalleled rejuvenation results. These findings were confirmed by analyzing the epigenetic age of rats’ DNA and measuring IgG glycans – markers of cell state – which suggests that pig plasma treatment could play an integral part in future therapies capable of reverse biological aging.

They Reverse the Age of the Liver

The liver is a resilient organ, yet prolonged stress and overwork can damage it to an irreparable degree, leading to scarring and eventually liver failure. Scientists are constantly exploring new methods for reinvigorating regenerative abilities of the liver.

One of the most effective approaches is using young pig blood as an anti-ageing treatment. Young blood contains high concentrations of anti-ageing molecules such as exosomes – small vesicles that transport DNA between cells – that may also protect liver tissue from inflammation or damage.

Scientists were delighted to find that when they conducted tests using this pig plasma treatment on various rat tissues, it worked – dramatically reducing epigenetic age in several organs such as heart and liver while even seeing signs of rejuvenation in hypothalamus of brain.

Interesting evidence indicates that liver cells may possess their own set of unique regenerative mechanisms. Hepatocytes and cholangiocytes appear to retain their telomere length throughout aging due to a lower turnover rate that preserves their potential regenerative potential.

Researchers conducted this research and observed that treatment with pig blood significantly reduced the epigenetic age of hepatocytes in treated rats, along with an increase in protein acetylation and sirtuin 1 activity that promoted regeneration capacity of these cells.

This research brings us a step closer to reversing the aging process for humans. However, more work remains before harnessing hepatocyte regenerative powers to lengthen lives. For now, it’s important to be aware of risks associated with hepatocellular regeneration mechanisms and seek medical treatment if you experience any health problems related to them.

They Reverse the Age of the Blood

Researchers observed that plasma fraction therapy significantly reduced the epigenetic ages of blood, liver, and heart tissue from old rats to levels comparable with young ones; this effect was also observed in their hypothalamus. Furthermore, this treatment raised levels of three key antioxidants such as glutathione, catalase, and superoxide dismutase that are known to protect against reactive oxygen species (ROS) generated from shortening telomeres and other mechanisms of cell senescence.

ROS have long been recognized as being a major cause of organ and cell aging. Research has also demonstrated that eliminating senescent cells through genetic or pharmaceutical means improves health and extends longevity in mice [Faragher et al. 2017].

Scientists from the University of California created conjoined twin mice out of young and old mice and observed that their joint organs were rejuvenated by blood from their shared young donor – leading them to produce and trial therapeutics based on this idea that infusions of youthful plasma could renew ageing cells and tissues [Rando & Jones 2021].

The new study builds upon these discoveries. Researchers treated young and old Sprague Dawley rats for seven to 10 months using Yamanaka factors, measuring hematological and biochemical indices of aging at regular intervals. After this treatment period ended, DNA methylation profiles from multiple organs in both groups were analysed to generate epigenetic ages for each organ compared with control rats obtained from their trunks – and plasma fraction therapy significantly lowered them all.

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