Science and Longevity
Creating Temporal Bridges in Experimental Biology for Longevity
Understanding the exciting concept of heterochronic parabiosis
I have studied longevity within brain health and cognitive function perspectives for decades. During my studies, I came across many exciting concepts. One of them is heterochronic parabiosis.
I see heterochronic parabiosis as a biological time-travel experiment, exploring whether the blood of the young can favorably impact the aging process in the old and vice versa. It’s a fascinating concept with the hope of finding new ways to promote better health and longevity for older folks.
Heterochronic parabiosis is a scientific term that describes an experimental setup where two animals of different ages are surgically connected, creating a shared circulatory system between them. This process allows them to exchange blood and the molecules they carry.
The process at the conceptual level can be seen as a comprehensive version of the transbiosis concept in biotechnology involving transferring cells, tissues, or entire body parts from one organism to another.
Early experiments connected two animals of the same species to study the effects of shared blood circulation. These experiments aimed to investigate factors like nutrient exchange and immune response.
Researchers hypothesize that certain factors in young blood might promote tissue regeneration, enhance cognitive function, and improve overall health in the older partner. Conversely, factors in old blood might negatively affect the younger partner’s physiology. So, it looks like a win-lose situation.
The critical focus of heterochronic parabiosis is on the blood. Blood contains many signaling molecules, hormones, and cells.
The compelling idea is that the young blood from one partner can favourably influence the physiology of the older partner, potentially slowing down the aging process.
So far, most heterochronic parabiosis studies have been conducted in mice and rats due to their genetic similarity to humans. For instance, a young mouse is surgically connected to an older mouse, allowing blood exchange between them.
While some studies have shown promising results, with signs of rejuvenation in older animals, some experiments haven’t replicated these findings, and there’s ongoing debate about the specific factors responsible for the observed effects. So, the field is still evolving.
The idea behind these studies is to identify specific factors in the blood that contribute to aging or rejuvenation and develop targeted interventions. So, if the experiments prove successful, they could open new therapeutic avenues for age-related conditions. Some believe that this is the secret to the fountain of youth.
The primary impact under investigation is on the prevention of aging. Researchers aim to understand whether factors present in young blood can have rejuvenating effects on tissues and organs in older partners. Conversely, they explore if factors in old blood might accelerate aging in the younger partner.
As with any scientific breakthrough, there are ethical considerations. The translation of findings from animals to humans must be approached cautiously. What works in mice may not necessarily work the same way in humans. I believe there will be many more ethical factors that researchers need to clear before trying the concept on humans.
Following this introduction, I’ll offer a brief historical background, share insights from scientific studies, and present interpretations in straightforward language, aiming to inform you about this exciting concept.
An Overview of Historical Background for Heterochronic Parabiosis
In the 1950s and 1960s, David Harrison, a pioneer in the field, conducted significant experiments on parabiosis in rats. By connecting old and young rats, he observed physiological changes in both, suggesting that factors in the blood could influence the aging process.
During the 1980s and 1990s, the perspective on aging evolved as researchers delved into the roles of specific molecules, hormones, and cells in the aging process. This era laid the foundation for a deeper molecular understanding of how aging manifests at cellular and systemic levels.
Heterochronic parabiosis, specifically studying animals of different ages, gained momentum in the early 2000s. Researchers started focusing on the potential rejuvenating effects of young blood on aged tissues. Studies in mice became particularly prominent, exploring the impact on various organs and cognitive function.
Irving Weissman and his team at Stanford University conducted influential experiments in 2005. They connected the circulatory systems of young and old mice and observed improvements in the regenerative capacity of muscle and liver in the older mice. This study suggested that young blood might contain factors promoting tissue regeneration.
In 2013, researchers pinpointed Growth Differentiation Factor 11 (GDF11) as a promising rejuvenating factor. Studies indicated that GDF11 levels declined with age, and restoring these levels in elderly mice resulted in enhancements in both muscle and brain function.
Despite encouraging discoveries, the field encountered controversies and challenges. Some studies encountered difficulties replicating the rejuvenating effects, and uncertainties arose about the specificity of the factors contributing to observed outcomes.
The intricacies of the aging process and the multitude of substances in blood presented challenges in pinpointing exact mechanisms.
Ongoing research in heterochronic parabiosis aims to identify the specific blood factors responsible for observed effects and explore potential applications in treating age-related diseases. Ethical considerations have gained prominence, emphasizing caution in translating findings from animal studies to human applications.
In summary, the historical journey of heterochronic parabiosis has evolved from early experiments exploring shared circulation to current molecular investigations into factors influencing aging. Despite facing challenges and controversies, the field holds promise for unraveling the complexities of aging and exploring potential therapeutic interventions.
Brief Insights from the growing literature
The studies from credible sources I reviewed cover various aspects of heterochronic parabiosis, like its effects on cognitive function, neural stem cells, and tissue repair.
To stay updated on the latest in this dynamic field, check out newer studies and reviews, as they may replace older approaches.
This 2013 comprehensive review examines the history of heterochronic parabiosis, the methods used, and the significant discoveries made through these studies, especially in understanding the aging of stem cells.
It informs that “Pairing two animals in parabiosis to test for systemic or circulatory factors from one animal affecting the other has been used in scientific studies for at least 150 years.”
According to the paper, “While animal grafting experiments may date back to medieval or ancient times, the earliest widely recognized publication on parabiotic pairings is Bert’s study titled ‘Expériences et Considérations Sur la Greffe Animale,’ published in French in 1864.” It means “Experiments and Considerations on Animal Grafting [transplantation].”
This paper in Nature informs that as tissues age, their regenerative ability declines, often due to changes in tissue-specific stem cells. For instance, aged muscle experiences impaired regeneration due to reduced Notch signaling in satellite cells. In the liver, decreased hepatic progenitor cell proliferation hampers regenerative capacity.
To understand how systemic factors influence aged progenitor cells, researchers conducted heterochronic parabioses (shared circulatory system) between young and old mice. This exposed old mice to factors in young blood.
The study found that this approach restored Notch signaling, increased satellite cell activation and proliferation, and improved aged hepatocyte proliferation. The results suggest systemic factors play a role in modulating the decline in progenitor cell activity associated with aging.
As human lifespan increases, more people face age-related cognitive impairments, underscoring the need to understand how to mitigate aging effects. To this end, researchers who published this paper in Nature found that exposing aged animals to young blood can counteract and reverse existing effects of brain aging at molecular, structural, functional, and cognitive levels.
The paper informs that “Genome-wide analysis of young and aged animals with connected circulatory systems revealed synaptic plasticity-related transcriptional changes in the aged hippocampus.”
Researchers found an increased dendritic spine density, improved synaptic plasticity, and enhanced cognitive performance. Activation of the cyclic AMP response element-binding protein in the aged hippocampus partly mediated these improvements, indicating that exposure to young blood can rejuvenate synaptic plasticity and cognitive function in aged mice.
Another paper in Nature stated that “Aging is a significant risk factor for neurodegenerative diseases, and parabiosis experiments have shown that exposure to young blood enhances the brains of older mice. Previous research indicated that Growth Differentiation Factor 11 (GDF11) in the bloodstream increases neural stem cells and improves vasculature in the subventricular zone of old mice.
So, their newer study reveals that GDF11 enhances neurogenesis in the hippocampus, improves vasculature, and increases markers of neuronal activity and plasticity in the hippocampus and cortex of aged mice.
Researchers found that GDF11 exerts its effects by acting on brain endothelial cells, targeting the cerebral vasculature instead of crossing the blood-brain barrier. This distinct mechanism sets GDF11 apart from other circulating factors that enhance central nervous system function without directly entering the CNS.
This 2018 study in CJI Insight informs that “Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis.”
Their research used genetic tracing to confirm that proximal tubular epithelial cells don’t become myofibroblasts. Yet, in parabiosis models, where one individual was labeled and the other had kidney fibrosis, they found a few renal myofibroblasts from the circulating cells.
The sequencing showed these cells are monocytes expressing inflammatory signals, hinting at a role in renal fibrosis through signaling rather than direct action.
Monocytes are a type of white blood cell that plays a crucial role in the immune system. They are involved in the body’s defense against infections and other immune responses.
In this 2022 study in Cell pairing old and young mice, improvements were observed in senescent and apoptotic cells, reduced inflammation in the liver, and reduced fibrosis in the liver and spleen. Skeletal muscle and skin showed rejuvenation, with restored muscle fiber diameter and increased hair follicles, indicating a more youthful state. The study highlights systemic influences on aging and rejuvenation.
This 2023 study in the International Journal of Molecular Sciences informs that extracellular vesicles (EV) in young serum contribute to restoring age-related brain transcriptomes and cognition in old mice.
Their analysis reveals that EVs impact genes related to barrier function and transport in the choroid plexus, leading to reverse transcriptomic aging. Treatment with young blood upregulates the anti-aging gene Klotho in the hippocampus, and this effect is diminished without EVs.
The study underscores the role of EVs in transmitting signals from the periphery to the brain and emphasizes Klotho’s importance in maintaining brain homeostasis.
What do these complex studies mean to my readers?
Researchers have been investigating the mysteries of aging and regeneration through heterochronic parabiosis, where young and old animals share their circulatory systems, which I introduced in this article.
This unique approach has shed light on various aspects, from cognitive function and tissue repair to the decline in regenerative abilities as tissues age. Essentially, scientists are exploring how factors in young blood might hold the key to slowing down or reversing aging effects in older animals.
One fascinating discovery relates to the impact of young blood on the brain. Connecting the circulatory systems of young and old animals seems to improve synaptic plasticity, dendritic spine density, and overall cognitive performance in aging brains.
This concept is like a rejuvenating boost for the mind, suggesting that there’s something special in youthful blood that can counteract the effects of aging on the brain.
Another exciting finding involves a protein called Growth Differentiation Factor 11, which appears to enhance neurogenesis and improve vasculature in aged mice. Unlike other substances circulating in the blood, GDF11 specifically targets the blood vessels in the brain, showcasing a unique mechanism that could positively impact the central nervous system in aging people.
The focus is on tiny structures called extracellular vesicles found in young blood. These vesicles seem to carry signals that impact the genes related to brain health. Researchers found that these vesicles contribute to restoring cognitive function in older mice, emphasizing their crucial role in maintaining a healthy balance in the brain.
Some studies explore how specific immune cells (monocytes) might play a role in kidney fibrosis. While it’s known that specific cells in the kidney contribute to scarring, scientists have discovered that a small fraction of these cells may come from the bloodstream, specifically monocytes.
These cells seem to communicate signals contributing to kidney fibrosis, highlighting the intricate ways different body parts interact.
Kidney fibrosis happens when the kidneys develop excess scar tissue in response to injury or damage. This scar tissue replaces normal, functional kidney tissue and can lead to a loss of kidney function over time.
It’s a common consequence of various kidney problems, disrupting the kidneys’ ability to filter waste and fluids from the blood effectively.
Kidney fibrosis can ultimately result in chronic kidney disease, a severe and irreversible condition. Understanding the causes and processes behind kidney fibrosis is essential for finding ways to prevent or treat chronic kidney diseases.
In simple terms, these studies collectively suggest that there’s something special in young blood that can positively influence aging-related issues, from cognitive decline to tissue regeneration, and it opens up new possibilities for understanding and potentially addressing the aging process.
Conclusions
Heterochronic parabiosis is an exciting and complex concept in aging and longevity studies. While it holds promise for understanding the role of blood in aging and rejuvenation, much research is still needed to grasp the intricacies and potential applications in human health.
Researchers fine-tune the approach, identifying the specific factors responsible for the observed effects. This includes exploring the role of specific proteins, cells, hormones, and signaling pathways in the blood.
In simple terms, heterochronic parabiosis is like a biological time-travel experiment, exploring whether the blood of the young can impact the aging process in the old and vice versa.
It’s an intriguing journey where biology intersects with aging, offering the promise of discovering novel ways to enhance health and longevity.
A medical doctor, Hendy Wijaya, MD, recently posted an article to one of my publications titled Blood, Legends, and the Quest for Eternal Youth. Dr Wijaya concluded that “Since these findings were published, Tom Rando’s laboratory at Stanford University, where Conboy conducted her parabiosis research, received numerous phone calls. People asked, “Have you just discovered the secret to staying young?”
While I’m not sure parabiosis can be a reality for humans in my generation as it is a still conceptual idea, I’ve found my fountain of youth through healthy lifestyle choices — maintaining a balanced diet with whole foods with time-restricted eating, regular movement, restorative sleep, downtime, long-term fasting, thermogenesis, and meditation.
Thank you for reading my perspectives. I wish you a healthy and happy life.
To inform my new readers, I wrote numerous articles that might inform and inspire you. Some topics I cover are brain and cognitive function, significant health conditions, valuable nutrients, ketogenic lifestyle, self-healing, weight management, and humor.
I contribute to multiple publications but keep my health and wellness stories on EUPHORIA. My posts do not include professional or health advice. I only document my reviews, observations, experiences, and perspectives to provide information and create awareness.
To get my post in your inbox, you may subscribe to my content. If you are a writer, you are welcome to join my publications as a writer by sending a request via this link. I support 24K+ writers who contribute to my publications on this platform. I also write about technology, business, and leadership from a different profile. Here is a sample curated collection.
