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Parabiosis refers to the surgical joining of two animals, usually mice or rats, but sometimes even monkeys, in such a way that their circulatory systems become interconnected. This allows the blood and other biological fluids of the two animals to mix and flow between them. This method is sometimes subject to criticism by scientists due to ethical concerns for animals.

Parabiosis and aging

Parabiosis is often used in biological research as a way to study the effects of aging or disease on the body, based on the hypothesis that blood-borne factors might have effects on lifespan, healthspan or tissue function.[1]

Heterochronic parabiosis

A special type of parabiosis, heterochronic parabiosis (HPB), involves pairing a young and an old organism, in order to study the effects of systemic factors on aging. In recent years, this experimental approach has seen a resurgence, with numerous studies proposing that young systemic factors have rejuvenating effects in tissues such as the nervous system, muscles, heart or liver. However, the exact nature of the circulating molecules that drive these effects remains largely unknown.

Extended HPB treatment (3 months), followed by a 2-month detachment period led to lifespan extension in old mice subjected to HPB, when compared to control isochronic mice (mice surgically joined to another mice of the same age).[2] Biological age markers based on epigenetic tests showed a rejuvenation of blood and liver tissues in old mice undergoing HPB.

An optimised protocol por parabiosis was recently developed in which two mice are internally united at the elbow and knee joints with continuous external joining of the skin, while addressing some common complications like variable sensitivity to anaesthesia, dehydration or weight loss.[3]

A study performing single-cell RNA sequencing on 20 organs after heterochronic parabiosis, found that fat cells, liver cells and blood cells were amongst the cell types more responsive to the intervention.[4] The same study found there was an increased expression of genes involved in mitochondrial metabolism in old mice.

List of blood factors believed to influence aging

1. Extracellular vesicles (mainly exosomes - the so-called E5 fraction[5][6][7]);



  1. Ashapkin VV, Kutueva LI, Vanyushin BF. The Effects of Parabiosis on Aging and Age-Related Diseases. Adv Exp Med Biol. 2020;1260:107-122. doi: 10.1007/978-3-030-42667-5_5. PMID: 32304032.
  2. Zhang, B. et al. (2021) “Multi-omic rejuvenation and lifespan extension upon exposure to youthful circulation.” Available at:
  3. Rodriguez, S.L. et al. (2022) “An optimized mouse parabiosis protocol for investigation of aging and rejuvenative mechanisms,” Frontiers in Aging, 3. Available at:
  4. Pálovics, R., Keller, A., Schaum, N. et al. Molecular hallmarks of heterochronic parabiosis at single-cell resolution.Nature 603, 309–314 (2022).
  5. Horvath, S., Singh, K., Raj, K., Khairnar, S., Sanghavi, A., Shrivastava, A., ... & Katcher, H. L. (2023). Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction. bioRxiv, 2023-08. PMID: 37609328 PMC10441355 DOI: 10.1101/2023.08.06.552148
  6. Dan Xu, Hidetoshi Tahara. (2013). The role of exosomes and microRNAs in senescence and aging. Advanced Drug Delivery Reviews. 65, 368-375;
  7. Takasugi, M. (2018). Emerging roles of extracellular vesicles in cellular senescence and aging. Aging cell, 17(2), e12734. PMID: 29392820 PMC5847882 DOI: 10.1111/acel.12734