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Episode 2 — The Prospect of Immortality & Human Cryopreservation

Host: Kyle O’Brien — https://twitter.com/analog_kyle.

Guest: Emil Kendziorra — https://twitter.com/emilkendziorra.
Founder of @TomorrowBio.

Theme || the prospect of immortality & human cryopreservation.

Is Death just a Technical Problem we haven’t solved yet?

In this episode of State Change, Kyle O’Brien sits down with Emil Kendziorra, founder of Tomorrow Bio, to explore the science, ethics, and future of cryopreservation — the process that may one day allow humans (and even pets) to be revived centuries from now.

We talk about the brain, identity, consciousness, why people fear death, and what it means to rewrite the social contract when life extension becomes real.

Continue reading “Episode 2 — The Prospect of Immortality & Human Cryopreservation” | >

Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification

Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.

The authors have declared no competing interest.

Scientists Discover Natural Compounds With Unexpected Benefits for Skin, Anti-Aging, and Heart Health

Natural UV-protective compounds from algae are revealing unexpected biological activities. Scientists have found that certain natural compounds produced by algae and cyanobacteria may offer benefits beyond sun protection, including support for skin health and cardiovascular function. In lab experim

Scientists Identify Key Protein That Could Reverse Brain Aging

The study findings also suggest approaches that enhance expression or activity of DMTF1 may have therapeutic potential in reversing or delaying aging-associated decline of neural stem cell function.

While the preliminary findings stemmed mainly from in vitro experiments, the researchers hope to explore if elevating DMTF1 expression can regenerate neural stem cell numbers as well as improve learning and memory under the conditions of telomere shortening and natural aging, without increasing the risk of brain tumors. The long-term objective is to discover small molecules that can enhance DMTF1 expression and activity to improve the function of aged neural stem cells.

“Our findings suggest that DMTF1 can contribute to neural stem cell multiplication in neurological aging,” Dr Liang said. “While our study is in its infancy, the findings provide a framework for understanding how aging-associated molecular changes affect neural stem cell behavior, and may ultimately guide the development of successful therapeutics.”

Skeletal Muscle Aging and Stem Cells

Aging impairs the regenerative capacity of skeletal muscle in part through the functional decline of the resident stem cell population called satellite cells. With age, satellite cells exhibit a loss of quiescence, altered proliferation, and impaired differentiation, leading to incomplete myogenesis following injury. Mitochondria are central to stem cell function, providing ATP, regulating redox homeostasis, and integrating several signaling pathways during lineage progression. While mitochondrial remodeling and function is essential for supporting the metabolic demands of myogenesis, the extent to which these processes are altered in aged satellite cells across cell states remains unclear. To address this, we performed a comparative transcriptomic analysis of young and aged satellite cells in quiescent, proliferating, and early differentiating states using three publicly available microarray datasets. Our results reveal that aged satellite cells exhibit a dysregulated senescence profile, characterized by the simultaneous upregulation of both senescence-inducing and-inhibiting genes, suggestive of a metastable senescence state. These features persisted during early differentiation, where aged cells also displayed increased expression of senescence-associated secretory phenotype (SASP) components, potentially contributing to a pro-inflammatory niche. Mitochondrial gene expression was relatively stable in quiescent cells but showed marked remodeling upon activation, particularly in aged cells. While young satellite cells upregulated transcriptional programs related to mitochondrial function, aged cells exhibited broader and less coordinated responses enriched for stress, apoptotic, and metabolic pathways. Despite evidence of mitochondrial stress, mitophagy gene activation remained limited in aged cells, raising the possibility of impaired organelle quality control. Together, our findings highlight age-associated disruptions in both senescence and mitochondrial remodeling programs across the satellite cell lifecycle. These transcriptional changes likely underlie impaired regenerative responses in aging muscle and identify potential targets for rejuvenating muscle stem cell function.

Aging is accompanied by a progressive and multifactorial decline in the function of virtually all physiological systems, contributing to increased frailty, disease burden, and reduced regenerative capacity in older individuals (López-Otín et al., 2013; Dodig et al., 2019; Tenchov et al., 2023). While this decline reflects the combined effects of genomic instability, proteostatic stress, metabolic alterations, and chronic low-grade inflammation, a critical component of age-associated tissue deterioration is the loss of stem cell function (López-Otín et al., 2013; Dodig et al., 2019; Tenchov et al., 2023). Adult stem cell populations are essential for tissue maintenance and regeneration throughout life, replenishing differentiated cells during homeostasis and responding to injury with rapid expansion and lineage-specific differentiation (Hawke and Garry, 2001; Dumont et al., 2015b; Dumont et al., 2015a).

From organoid culture to manufacturing: technologies for reproducible and scalable organoid production

Despite the absence of a fully established regulatory framework or unified technological standard for industrial-and clinical-grade organoid biomanufacturing yet, substantial progress has been made toward building the technical and institutional infrastructure required for scalability and reproducibility. The Organisation for Economic Co-operation and Development (OECD) introduced the Good In Vitro Method Practices (GIVIMP)19, an international quality-assurance framework that defines laboratory quality systems, method qualification, reference controls, equipment calibration, and data integrity—principles that now potentially serve as quantitative benchmarks for process validation in organoid production. Complementing this, the NIH Standardized Organoid Modeling (SOM) Center was recently established to promote the development of organoid platforms that are reproducible, robust, and broadly accessible for translational biomedical and pharmaceutical research.

Expanding these standardization efforts, a recent publication introduced the Essential Guidelines for Manufacturing and Application of Organoids, delineating a systematic workflow encompassing cell sourcing, culture optimization, quality control, and biobanking logistics20. Their framework identifies organ-specific critical quality attributes (CQAs)—including growth-factor composition, morphological fidelity, and quantitative analytical metrics—and recommends standardized cryopreservation conditions (~100–200 organoids per vial) to enhance batch comparability. Likewise, a recent study established quantitative criteria for human intestinal organoid standardization, specifying cell-line provenance, minimum lineage composition thresholds (e.g., ≥30% enterocytes), and molecular marker expression profiles consistent with physiological differentiation21. Taken together, these coordinated initiatives—from international organizations to national agencies and individual laboratories—represent an emerging global framework toward reproducible, quality-controlled, and scalable organoid biomanufacturing, laying the groundwork for eventual regulatory convergence and clinical translation.

In response to these prevailing limitations and in alignment with global standardization trends, a range of engineering strategies has been developed, shifting the paradigm from organoid culture to organoid manufacturing by enabling reproducible and scalable organoid production. These strategies broadly focus on two goals: improving reproducibility by minimizing uncontrolled variation in the culture environment as well as by regulating intrinsic morphogenetic processes, and enhancing scalability by increasing productivity and throughput. To this end, recent advances can be categorized into three major domains: cellular engineering approaches that regulate morphogenetic processes through programmed cell organization; material-based strategies that establish defined and controllable environmental cues; and platform-or system-level innovations that enable high-throughput and automated workflows. Together, these innovative engineering advances mark aion toward more standardized, efficient production workflows.

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