LongeCityNews Last Updated: 15 March 2026 - 01:59 PM

Startup biotech companies have started to use the publication of preprint scientific papers as a way to enhance their standing with investors; putting out a preprint is considerably faster than formal publication, and requires no review process. Many startups undertake programs of research and development that are novel enough to have little in the way of a foundation of prior scientific literature, and thus this is one area of scientific publication in which more weight than usual should be given to the peer review process. In particular, one should be skeptical regarding claims of very large extension of life span in animal models in preprint papers.

Yes, someone will turn up at some point with a surprising, novel approach to rejuvenation that is impressive in comparison to the past scope of slowed aging and extended life in mice, and perhaps that program will be wrapped in a biotech company, and perhaps they will want the benefits of publishing as soon as possible rather than waiting on review. That future seems inevitable, given the pace of progress in aging research and the trend towards opening and democratizing the peer review process. Nonetheless, extraordinary claims still require extraordinary evidence. The history of claimed extension of life span in mice is littered with failed replication, and particularly so for studies that used small numbers of mice and claimed a large extension of life.

The startup biotech program reported in today's preprint paper is conducted by Sentcell. It is interesting and novel enough for the rest of the world to be skeptical until much more work on the topic is published. The size of the reported extension of life in mice resulting from their novel therapy is very large relative to the best that can be achieved via established approaches; large enough to reduce the credibility of the work, especially given the small numbers of mice used per study group. The researchers claim to have isolated a particular subset of cell communications that induces rejuvenation, which in and of itself is reasonable. Many companies and research groups are indeed exploring how cells might change one another's behavior for the better. Consider that stem cell therapies produce benefits via the signaling of transplanted cells as one example among many. It is the size of gain in mouse life span reported here that calls for a far greater body of supporting evidence in order to be taken at face value, given how very much larger it is than the effects of, e.g. stem cell therapies, exosome therapies, senolytics, and so forth.

CD4+ T cells confer transplantable rejuvenation via Rivers of telomeres

One theory attributes ageing to the accumulation of terminally differentiated or senescent cells in multiple tissues, disrupting homeostasis. A true fountain of youth would need to target senescent cells across organs, be tightly regulated, and transfer youth-promoting activity from a young organism to an old one - as in the original parabiosis studies. One rejuvenation candidate arises from telomere transfer between immune cells. We previously showed that antigen-presenting cells (APCs) donate telomere-containing vesicles to CD4+ T cells during immune synapse formation, extending their telomeres, preventing senescence, and generating long-lived, stem-like memory T cells.

Here we show that, after telomere acquisition, recipient CD4+ T cells undergoing fatty acid oxidation, assemble and release "Rivers" of telomeres into the circulation. These Rivers recycle surplus APC telomeres unused by the T cells and rejuvenate tissues throughout the body, extending lifespan - an unprecedented programme in which CD4+ T cells transmit youth-promoting signals between organisms. While analysing antigen-specific T cell memory responses, we observed that APC telomere transfer was accompanied by abundant extracellular telomeric material. Histology revealed that these extracellular telomeres were not merely tethered to T cells but arranged in vessel-like networks, suggesting release into circulation. The elongated, punctate structures appeared to flow along these networks, evoking miniature streams of genetic material - henceforth referred to as telomere Rivers.

In aged mice, adoptive transfer of young or metabolically reprogrammed CD4+ T cells triggered River production in vivo, and Rivers isolated from these animals could be transplanted into other aged mice to propagate the rejuvenation phenotype independently of T cells. River therapy extended median lifespan by ∼17 months, with several mice surviving to nearly five years. This immune-driven telomere transfer pathway is conserved across kingdoms, including plants, defining the first systemic, transplantable programme of youth.

A new study suggests that microbiome remodeling is a mechanism behind age-related cognitive decline, with one particular bacterial species identified as the likely culprit. In mice, antibiotics seem to reverse this effect [1].

The gut-brain axis and the microbiome

Memory decline is a common and debilitating feature of aging, but its mechanisms remain poorly understood. The hippocampus, a brain region essential for forming, storing, and retrieving memories, gradually loses its ability to encode new information with age, and this is not fully explained by changes within the brain itself.

In recent years, the gut microbiome has emerged as a surprising factor in brain function. Several studies have shown that the microbiome changes with age and that transferring gut microbes from old animals to young ones could worsen cognition [2]. However, the anatomical and molecular pathways connecting intestinal bacteria to memory processing were largely undefined. In a new study published in Nature, researchers from Stanford University Medical Center offer an intriguing potential explanation.

I’ll give you my bacteria if you give me yours

The authors co-housed young and aged mice for one month. Co-housing in mice leads to microbial transfer, so the young mice acquire an “old-like” microbiome [3]. They then tested cognition using the novel object recognition (NOR) task, which measures short-term memory, and the Barnes maze, a spatial learning and memory test.

The performance of young mice co-housed with old mice was impaired on both tests. Importantly, physical frailty and exploratory behavior were unchanged, meaning that the mice were not just less active; they specifically could not form or retrieve memories as well. The effect was seen in both sexes and across mice from different vendors.

A series of experiments ruled out social effects. For instance, co-housing old and young mice under germ-free conditions did not impair cognition in the latter. Fecal microbiota transplantation (FMT) from aged donors into young germ-free mice recapitulated the cognitive impairment without any co-housing, directly implicating the microbiome. Germ-free mice showed delayed cognitive decline compared to conventionally colonized mice, still performing normally at 18 months.

Ablating the aged microbiome with broad-spectrum antibiotics before or during co-housing prevented the cognitive deficit. Strikingly, even administering antibiotics after the cognitive deficit developed reversed it, both in co-housed young mice and in naturally aged mice. All the results pointed to a microbial influence rather than social stress or aging per se as the cause of the transmissible cognitive decline.

Looking for the species and the mechanism

The researchers then tried to understand which gut bacteria are particularly responsible for this cognitive decline. Parabacteroides goldsteinii emerged as the top-ranked candidate. Its abundance increased with age, it was efficiently transmitted by co-housing and FMT, and germ-free or antibiotic-treated young mice monocolonized with P. goldsteinii developed cognitive impairment.

Features like neurogenesis and spine density were all normal in co-housed young mice; they changed in naturally aged mice but were not transmissible via the microbiome. However, RNA-seq revealed that immediate-early gene (IEG) expression – genes that are rapidly activated when neurons fire, such as Fos – was blunted in co-housed young mice, aged mice, and germ-free recipients of aged microbiota.

FOS staining confirmed reduced neuronal activation in the hippocampus in response to novel object exposure. Colonization with P. goldsteinii alone similarly suppressed hippocampal FOS responses. These results suggest that microbiome specifically impairs the brain’s ability to activate neurons in response to new experiences, rather than causing structural brain damage.

The research stained several brain regions for FOS and zeroed in on the nucleus tractus solitarius (NTS), a structure in the brainstem that serves as the primary receiving station for signals from the vagus nerve – the longest cranial nerve in the body, which innervates most of the visceral organs, including the entire gastrointestinal tract. By ablating and activating various neuronal subtypes, the researchers determined that it’s the vagus nerve that malfunctions and not spinal nerves, some of whom also transmit to the NTS.

Stimulating the vagus nerve restored cognition, confirming the vagal pathway’s importance. The cognitive deficit, however, was not caused by reduced gut hormone production. Something else was suppressing vagal function, so, the researchers searched for a different mechanism.

Medium-chain fatty acids are the key

The liquid that surrounded P. goldsteinii and contained its secreted molecules (its supernatant) was sufficient to impair cognition. Metabolomics helped attribute this effect to the medium-chain fatty acids (MCFAs) that P. goldsteinii produces. Intestinal MCFA levels increased with age in conventionally colonized but not germ-free or antibiotic-treated mice and were transmissible by co-housing.

The authors then screened viruses that infect bacteria (bacteriophages) for their ability to restore memory in aged mice. One phage, φPDS1, which is known to target a different bacterial genus, consistently improved cognition in aged mice. Apparently, the phage works not by killing P. goldsteinii but by altering its gene expression in ways that reduce MCFA production.

GPR84 is a cell-surface receptor known to be activated by MCFAs. GPR84-deficient mice were resistant to cognitive decline, establishing GPR84 as the receptor through which MCFAs exert their effects on cognition. However, single-cell RNA sequencing of intestinal immune cells showed that Gpr84 is expressed exclusively by myeloid cells, such as macrophages, monocytes, and neutrophils, as opposed to microglia, the brain’s resident immune cells, or lymphocytes. This key distinction means that the inflammatory process driving cognitive decline is happening outside the brain.

Finally, the authors showed that the inflammatory cytokines TNF and IL-1β are the downstream effectors of GPR84 signaling that actually impair vagal function. Exogenous TNF or IL-1β was sufficient to impair cognition, and this was reversible by vagal stimulation. Deleting the IL-1β receptor specifically on vagal neurons blocked MCFA’s effect on memory, and forcing those neurons to fire anyway was sufficient to bypass the inflammatory blockade.

“Although memory loss is common with age, it affects people differently and at different ages,” said Christoph Thaiss, Ph.D., assistant professor of pathology. “We wanted to understand why some very old people remain cognitively sharp while other people see significant declines beginning in their 50s or 60s. What we learned is that the timeline of memory decline is not hardwired; it’s actively modulated in the body, and the gastrointestinal tract is a critical regulator of this process.”

“The degree of reversibility of age-related cognitive decline in the animals just by altering gut-brain communication was a surprise,” she added. “This study indicates that we can enhance memory formation and brain activity by changing the composition of the gastrointestinal tract – a kind of remote control for the brain.”

Literature

[1] Cox, T.O., Devason, A.S., de Araujo, A. et al. (2026). Intestinal interoceptive dysfunction drives age-associated cognitive decline. Nature

[2] D’Amato, A., Di Cesare Mannelli, L., Lucarini, E., Man, A. L., Le Gall, G., Branca, J. J., … & Nicoletti, C. (2020). Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity-and neurotransmission-related proteins in young recipients. Microbiome, 8(1), 140.

[3] Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., … & Gordon, J. I. (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341(6150), 1241214.

The chemistry of structural proteins in the lens of the eye changes with age in ways that render the lens less flexible, contributing to vision issues such as presbyopia, and eventually degrade its transparency. Age-related cataracts are the outcome of chemical alterations that cloud the lens and eventually lead to blindness. Better understanding the chemistry involved in this loss of transparency should hopefully lead to ways to replace the problematic molecular structures, or at least help to prevent the early stages of their formation. This is more challenging for the lens of the eye than is the case for most tissues that become damaged with age, as there is at best very limited natural replacement of the structural proteins of the lens. At present, replacement approaches are focused on surgery to replace the lens rather than any sort of nanoscale, chemical intervention that preserves the existing tissue.

The human eye lens plays an essential role in vision by focusing light onto the retina. This transparent tissue consists of densely packed crystallin proteins that exhibit remarkable solubility despite minimal protein turnover. Unlike most proteins, which are continuously recycled, crystallins must remain stable and soluble throughout the human lifespan. Aging causes damage to the lens, primarily via photochemical oxidation. Over time, this causes crystallin aggregation and leads to cataract.

Although understanding oxidative damage is critical to understanding cataract formation and how it can be prevented, it is difficult to study in native biological systems. Here, we use genetic code expansion to introduce an oxidation product, 5-hydroxytryptophan (5HTP), in a key site in human γS-crystallin, enabling it to be specifically investigated under controlled conditions. Replacing a critical tryptophan residue with 5HTP leads to reduced stability and increased aggregation.

Link: https://doi.org/10.1016/j.bpr.2026.100251

Take an aging population and a measure of function, and on average that measure will decline over time. That is degenerative aging in a nutshell, a loss of function, eventually including the very important function of staying alive. Within the environment of an average decline, however, it is possible to find individuals who manage to improve function between time points. Consider that it is well demonstrated that even very old people can improve capacity and reduce mortality risk by undertaking programs of structured exercise and strength training, for example. Few of us are exercising to an optimal level.

A widespread assumption exists among scientists, health care providers, and the public that later life is a time of inevitable and universal cognitive and physical decline. This assumption is likely due to considering older persons who improve to be exceptions, and the reliance on aging-health measures that do not allow for improvement. In contrast, we utilized a measure that allowed for an upward trajectory to occur. Our objective was to examine whether a meaningful number of older persons improve with this measure and, if so, to examine whether a promising modifiable culture-based variable, positive age beliefs, contributes to this improvement.

Individuals 65 years and older, who participated in a nationally representative longitudinal study, had their physical health assessed by walking speed and their cognitive health assessed by a global performance measure. We calculated the percentage of the sample that showed improvement in each domain from baseline to the last measurement up to 12 years later. We also examined whether a positive-age-belief measure predicted this improvement in regression models. It was found that 45.15% of persons improved in cognitive and/or physical function over this period, and positive age beliefs predicted these two types of improvement, both with and without adjusting for relevant covariates.

Link: https://doi.org/10.3390/geriatrics11020028