An Update from the Research Team – February 2023
Science is a never-ending process of learning and discovery. We, as scientists, are always looking for new ways to learn about the world around us and improve our understanding of the universe. This process of continuous research is what makes science so exciting and dynamic. As we look to evolve our experiments to better understand the impact of meditation on the human condition, we consider again the community that is present at the weeklong events. The Nashville Week-Long Event planned for April 2023 will see the launch of the PAIR (Partnering Age groups Into Resilience) Study. We have invented and will advance the concept of “mental parabiosis.” Can young and not-so-young minds engage in intense mental work and social engagement throughout the week to evolve their biology?
parabiosis/ [ par-uh-bahy-oh-sis]/ biology/ noun/ from the Greek words, para “besides” and bios “life.” (1) The natural union of two individuals, such as Siamese twins, so that they share a common circulation of the blood. (2) A similar union induced for experimental or therapeutic purposes.
Parabiosis allows researchers to show that the biological systems and environment created in one organism can affect a second organism, typically by the sharing and exchanging factors in the blood, such as plasma. A French scientist, Paul Bert, pioneered these studies in the mid-1800s, suggesting that organisms could be grafted together to enhance resilience.
Since these early beginnings, parabiosis and its impact on health and disease have been explored intensely over the last century focusing on metabolism, obesity, stem cell biology, tumor biology, diabetes, organ transplantation, among many others. More recent studies assessed the impact of heterochronic (different times/ages) parabiosis in linking young and aged animals.1 Young-aged systemic pairings result in the rejuvenation of aged cells and show that transferring aged components to young animals can dramatically impact processes such as neuronal plasticity.2,3 Pregnancy is a natural extension of such concepts where the exchange of fetal (young)-maternal (aged) environment results in the rejuvenation of the mother.4 Important work has shown that the transfer of these components does not necessarily depend on systemic pairing but can be affected by blood transfer.3,5 Whole blood is a complex mix of formed (i.e., red and white blood cells and platelets) and non-living (i.e., plasma) elements that can be further divided into sub-components (cellular subtypes, nutrients/metabolites, proteins, amino acids, lipids, electrolytes, gases, etc.) each capable of inducing biological effects. Much of our current research has shown that the blood of meditators is “different” after a week-long experience and is enriched in factors that can be transferred to other living systems to impact biology (i.e., inhibition of SARS-CoV-2 infection [manuscript in review], cancer cell biology).
Exploration of molecular mechanisms related to heterochronic blood exchange (HBE) changes have suggested the involvement of tumor growth factor-β, beta-2-microgloublin, alteration in stem cell niches, changes in the immune environment, oxytocin, senescence markers, hormones, altered Notch signaling, and potentially mitochondrial factors.2,5-11 The pioneering work in HBE has established an important characteristic about young and old organ systems. Organs at various ages have “plasticity” that can be functionally altered by factors in the blood and the circulatory environment. However, the transfer mediators and vehicles for molecular exchange in HBE are poorly understood. The cellular/organ origin of the transfer material, mechanisms of transfer, components of the transfer material, and ultimately the biologically active components are unclear. As we develop deep insights into the blood of meditators, we hope to define these factors better and determine what and why this mix of factors provides so much resilience in the pathological systems we have tested.
Age and Aging: A New Perspective
Age is relative. Organisms experience life capacity in very different time scales: C. elegans live 14-25 days, mice up to 2 years, humans in developed countries into their eighties, and yet there are some long-lived organisms such as the giant clam that can live upwards of 500 years. However, what is inevitable at the end of the life cycle of every organism is structural and functional decline observed at the cellular level. Multiple theories of aging have been proposed with no real consensus. A unifying theory of aging has been elusive. However, several ideas have been proposed to account for the aging deficit in efficiency and function. Though the mechanisms are unclear, they likely involve abnormalities that are a combined result of genetic, biochemical, catabolic, and physiologic deficiencies. The quest for the “fountain of youth” has been long-lived, where science has taken on this quest to discover causative factors leading to the derangement of biological systems with age to define a molecular parallel. Genetic tools have allowed us to test generations of cells and organisms for gain and loss of function. Many genes are considered critical if they show embryonic lethality, but such genes may only be important in the development and reproductive fitness with little impact on healthy aging. A reductionist approach to aging must take a different tact and define the early window of function in the context of what happens later in life using basic elements of life as a starting point. This endeavor presents several barriers that have ultimately limited the translation of ideas into practice to allow for healthy aging. More recently, the concept of distinguishing between “biological” vs. “chronological” age has emerged, suggesting that age is truly relative. We can live and experience unique environments to turn back the aging clock of our biology.
Physically across the world, “Blue Zones” have been identified12, where inhabitants in these areas live longer lives than average. Many studies have been done in these regions to determine what the longevity factors may be. As expected, diet (plant and legume heavy), physical activity, and no smoking are common features across these locations that may explain longevity, but less expected was the focus on family and social engagement. Humans are social creatures. When social creatures are deprived of these important interactions, there is a significant impact on physical, mental, and emotional health. The week-long meditation events are a case study in social experiments. The week starts with 1000+ individuals, many isolated and alone, that learn and grow together to become a community—a cohesive whole that is full of love, energy, vibrance, and resilience. Transformations happen, health evolves rapidly, and the whole becomes better than its parts. How and why?
Returning to our upcoming Pair Study, families are multi-generational and social engagement fosters connection. We will pair a young individual with an older individual. The pair will be linked throughout the week, meditating, socializing at meals, learning about each other, and evolving together. We have early evidence to show that twin pairs show connections mentally and physiologically when they are together and, amazingly, even when they are separated. The pairs in our study will be tested pre/post on EEG, be wearing Garmins, respond to health surveys, have blood collected, collect microbiome, undergo mitochondrial function/structure assessments, video record their experiences, and undergo cognitive tests (essentially a mini-QUANTUM study). We will track important biology about brain function, heart function, markers of biological age (Horvath clock), and many other assessments. The PAIR Study is expected to continue to advance our understanding of meditation on the individual and as the individual connects with the community.
1. Conboy MJ, Conboy IM, Rando TA. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 2013;12:525-530. doi: 10.1111/acel.12065
2. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760-764. doi: 10.1038/nature03260
3. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011;477:90-94. doi: 10.1038/nature10357
4. Popkov VA, Silachev DN, Jankauskas SS, Zorova LD, Pevzner IB, Babenko VA, Plotnikov EY, Zorov DB. Molecular and Cellular Interactions between Mother and Fetus. Pregnancy as a Rejuvenating Factor. Biochemistry (Mosc). 2016;81:1480-1487. doi: 10.1134/S0006297916120099
5. Rebo J, Mehdipour M, Gathwala R, Causey K, Liu Y, Conboy MJ, Conboy IM. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat Commun. 2016;7:13363. doi: 10.1038/ncomms13363
6. Conboy IM, Rando TA. Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle. 2012;11:2260-2267. doi: 10.4161/cc.20437
7. Conese M, Carbone A, Beccia E, Angiolillo A. The Fountain of Youth: A Tale of Parabiosis, Stem Cells, and Rejuvenation. Open Med (Wars). 2017;12:376-383. doi: 10.1515/med-2017-0053
8. Kiss T, Tarantini S, Csipo T, Balasubramanian P, Nyul-Toth A, Yabluchanskiy A, Wren JD, Garman L, Huffman DM, Csiszar A, et al. Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood. Geroscience. 2020;42:727-748. doi: 10.1007/s11357-020-00180-6
9. Pishel I, Shytikov D, Orlova T, Peregudov A, Artyuhov I, Butenko G. Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis. Rejuvenation Res. 2012;15:239-248. doi: 10.1089/rej.2012.1331
10. Sinha I, Sinha-Hikim AP, Wagers AJ, Sinha-Hikim I. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model. Cell Tissue Res. 2014;357:815-821. doi: 10.1007/s00441-014-1900-2
11. Yousefzadeh MJ, Wilkinson JE, Hughes B, Gadela N, Ladiges WC, Vo N, Niedernhofer LJ, Huffman DM, Robbins PD. Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues. Geroscience. 2020;42:951-961. doi: 10.1007/s11357-020-00185-1
12. Pes GM, Dore MP, Tsofliou F, Poulain M. Diet and longevity in the Blue Zones: A set-and-forget issue? Maturitas. 2022;164:31-37. doi: 10.1016/j.maturitas.2022.06.004