LongeCityNews Last Updated: 12 March 2026 - 01:09 PM

Some of the organs in the body do not have to be in their current location, nor structured in a single mass of tissue, in order to carry out all of their functions. The liver is one of these organs. Many (not all, but many) of the functions of the liver could be carried out by small amounts of liver tissue distributed throughout the body. Thus the existence of companies like Lygenesis, shepherding clinical trials of liver tissue organoid transplantation into lymph nodes to help restore lost function. Here, researchers report on the early stages of development for an alternative approach that is even less like normal liver tissue, essentially just an injection of cells and hydrogel rather than any production of structured tissue for transplantation, but that nonetheless produces a small volume of pseudo-tissue at the injection site that can carry out many of the functions of the liver.

Liver transplantation remains the standard treatment for end-stage liver failure, yet it is limited by donor scarcity, surgical complexity, and poor accessibility. Cell-based therapies offer an alternative, yet their translation has been hindered by low engraftment, poor localization, and a lack of delivery strategies that are both effective and minimally invasive. To address these challenges, we developed injected, self-assembled, image-guided tissue ensembles (INSITE), an injectable platform composed of primary human hepatocytes (PHHs) and hydrogel microspheres that assemble in situ into supportive, vascularizable scaffolds following image-guided delivery.

Ultrasound-guided delivery into an ectopic site enabled precise graft localization, persistent noninvasive imaging, and vascular integration in vivo. Hepatocytes remained confined within these scaffolds and maintained long-term functional activity. Furthermore, tuning material properties allowed control over scaffold remodeling and vascular recruitment to enhance graft function. By integrating image-guided delivery with a modular scaffold, INSITE establishes a clinically compatible strategy for advancing minimally invasive cell therapies.

Link: https://doi.org/10.1016/j.celbio.2026.100378

Researchers here mount an argument for aging to have evolved due to the interaction between (a) limited nutrient availability in the environment and (b) the options a cell has for generating the vital chemical energy store molecule adenosine triphosphate (ATP). Broadly, ATP can be generated via glycolysis in the cytoplasm or oxidative reactions in mitochondria, at least in eukaryotes such as mammals. Mitochondrial ATP production is slower and more energy-efficient, but both avenues decline with age. Loss of ATP production is harmful to cell and tissue function, most prominently in tissues with high energy needs such as muscle and the brain. Why does ATP production decline with age? The argument advanced here is that this decline evolved in part because it helps the survival of offspring by limiting parental consumption of resources, which borders on being a group selection mechanism. Group selection has long fallen out of favor, but a number of theories of aging, particularly those in the programmed aging category, have considered it to one degree or another.

Why do animals not have an eternal lifespan? Animals possess sophisticated systems that, in many species, appear capable of supporting immortality. Second, why do lifespans vary considerably among species despite similarities in genetic makeup, specifically the central dogma linking DNA, RNA, and protein synthesis, which warrants a molecular explanation? For example, elephants live thirty times as long as mice.

Significant differences between ATP production by glycolysis and oxidative phosphorylation include the quantity produced, production speed, and functional roles. Glycolytic ATP production is approximately 100 times faster than oxidative phosphorylation. ATP from glycolysis supplies rapid energy during acute demands, while oxidative phosphorylation supports basal/homeostatic cellular energy needs. Glycolysis plays important role in cell division and DNA repair. Additionally, the glycolysis activator HIF-1α promotes mitochondria repair through mitophagy. These findings suggest that decreased glycolytic ATP production during aging may underline various age-related symptoms. Immortal cells exhibit a metabolic profile characterized by highly active glycolytic ATP production and HIF-1α activation, even in oxygen-rich conditions.

Populations of species cannot grow infinitely, and one of the major limiting factors in natural world is food supply. The shift from glycolysis to aerobic metabolism increases energy efficiency, benefiting individual survival during food shortages, which can be caused by environmental changes or emergence of competitors for the food. This indicates that reduced glycolytic ATP production with aging can benefit the species by enhancing survival of parent generation at starvation conditions and allocating food to offspring generation in natural world where food supply is limited. Only species that happened to have an optimal rate of reduction in glycolytic ATP production over time were selected and survived through generational changes.

The optimal rate of glycolytic ATP decline for survival varies among species and depends on factors such as environment, competition, maturation time, and body size. This concept clarifies the significant differences in aging rates and lifespans across species despite largely conserved biological components. This is exemplified by the naked mole rat, an exceptionally long-lived species that lives underground where there are few environmental changes and predators, and maintains unrestrained glycolytic flux and ATP supply to adapt to underground life with low oxygen levels.

Link: https://doi.org/10.18632/aging.206356

Mitochondria are the power plants of the cell, vital to cell and tissue function. Mitochondria become damaged and dysfunctional with age, unfortunately, and this is thought to be a major contribution to age-related degeneration. That cells will take up mitochondria from the surrounding environment and put them to use has been established for some years. It is the basis for the development of mitochondrial transplantation therapies as a way to improve cell function in old tissues, delivering youthful mitochondria to augment the activities of native mitochondria that have been impaired by mechanisms of aging. Meanwhile, the research community continues to explore how exactly cells achieve uptake of mitochondria, as greater knowledge of the details may lead to ways to significantly improve on the coming first generation of mitochondrial transplantation therapies.

In today's open access paper, researchers report results from their study of how exactly the processes of endocytosis can be used to ingest mitochondria while preserving their structure and function. As a mitochondrion comes into contact with the exterior of the cell membrane, a region of the membrane wraps around the mitochondrion and then breaks off to bring it inside the cell, wrapped in an endosome. At some point the endosome is removed and the mitochondrion is fully internalized, intact and able to contribute to cell metabolism. This is a very high level description; there are a number of functionally distinct forms of endocytosis, and it appears that different types of endocytosis are used interchangeably for mitochondrial uptake, making it a more robust behavior.

Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells

Mitochondrial transplantation holds great promise as a therapeutic strategy; however, the mechanisms by which recipient cells interact with and internalize isolated mitochondria remain unclear. Therefore, in this study, we isolated functional mitochondria from mesenchymal stromal cells (MSCs) and characterized their biological activities and physicochemical properties. Additionally, effects of isolated mitochondria on MSC functions were evaluated.

Treatment with isolated mitochondria promoted cell proliferation, improved cellular viability under stress conditions, and increased the oxygen consumption rate, indicating enhanced bioenergetic capacity. Uptake of isolated mitochondria by MSCs was visualized via fluorescence imaging and quantitatively assessed over time, showing progressive internalization within 24 hours. To investigate the mechanism of mitochondrial uptake, endocytosis was chemically inhibited, which revealed that endocytic pathways contributed to the internalization of the isolated mitochondria.

These findings suggest that MSCs incorporate isolated mitochondria via active uptake mechanisms and that the internalized mitochondria retain their functional activity. Collectively, our results provide critical evidence of mitochondrial internalization in MSCs and offer insights into the potential applications of mitochondrial therapy for various diseases.

A recent study published in Geriatrics debunks the assumption that an older chronological age results in an inevitable and universal decline in health. The researchers reported that a significant number of older adults who participated in the study experienced an improvement in cognitive and/or physical functioning [1].

Challenging the status quo

Older age is known as a time of decline in both physical and cognitive health. Surveys have found that the vast majority of the general population, as well as health professionals, wrongly believe that everyone will develop dementia or that, as they age, their cognitive abilities will decline [2]. Even the tools used by the World Health Organization (WHO) to measure later-life cognitive and physical health only show whether there is or isn’t a decline, without the option for improvement [3].

Beyond not considering improvement as a possible outcome, there is also another reason the health improvements at older ages are not widely reported: researchers most often use average values to represent trajectories, and people who experienced improvements, if they are in the minority, do not show up in the results. “What’s striking is that these gains disappear when you only look at averages,” said lead author Becca R. Levy, a professor of social and behavioral sciences at the Yale School of Public Health (YSPH). “If you average everyone together, you see decline. But when you look at individual trajectories, you uncover a very different story.” Additionally, if some individuals show visible improvements, they are often viewed as exceptions rather than as part of a broader pattern [2].

The overall results perpetuates the idea that chronological aging leads to inevitable decline. However, this study challenges that assumption and presents evidence that improvement is possible, even at an older age.

Beyond extraordinary people

To give examples in support of the possibility of late-age improved performance, the authors start their paper with examples of people who achieved their biggest life achievements in later life, such as Diana Nyad, who, despite earlier failed attempts, at the ripe age of 64, set a world record in the 110-mile swim from Cuba to Florida.

Such anecdotes may lead to a conclusion that only very special, gifted individuals can improve with age. Therefore, these researchers analyzed data from a nationally representative Health and Retirement Study (HRS) of participants aged 65 and older to investigate whether improvement is possible even for the average person and “whether positive age beliefs predicted this potential improvement”.

In this study, physical health was assessed in almost 5,000 participants using walking speed, and global performance measures of cognitive health were collected in over 11,000 participants using a test that covers a broad range of cognitive domains, including short-term memory, delayed recall, and mathematical skills. The measures were taken at the beginning of the study and during follow-ups up to 12 years.

The power of belief

When the researchers in this study analyzed the study participants as a single homogeneous group, they observed, on average, declines in cognitive function and walking speed. However, upon closer, more granular examination, the researchers reported that, when analyzing a smaller subset of participants (those who had measurements of both walking speed and cognition), over 45% showed improved levels of cognitive and/or physical functioning beyond baseline, with many showing improvement in both domains. When analyzed separately, almost 32% of participants improved their cognition, and 28% improved their walking speed. A similar pattern of results was seen even with more stringent criteria.

Improvement in cognitive and physical health was predicted by the study participants’ positive age-related beliefs, even after adjusting for various factors and when more stringent criteria were applied to the analysis. Positive age beliefs associated with improvements were observed not only in participants who had some deficits at the beginning of the study (and were recovering from them) but also among people who had normal levels of functioning and improved beyond those levels.

In line with these results are the results of a previous study from this group that showed an association between negative age-related beliefs and biomarkers of Alzheimer’s disease, such as plaque and tangle accumulation, as well as lower hippocampal volume [4]. However, future studies should examine whether such an association exists between positive age-related beliefs and biomarkers of improved brain functioning, such as neurogenesis.

These results also agree with the stereotype embodiment theory (SET). According to this theory, the internalization of beliefs about old age begins at a young age and comes from various environmental sources. Those beliefs, when an individual becomes older, not only apply to others but also to oneself and can be used to predict better or worse cognitive and physical health [5].

Contradicting common views

The results of this study “contradict a dominant belief about aging held by scientists, health care professionals, and the lay public that it is a time of inevitable and universal decline in functioning.” This study provides additional evidence in support of previous studies that show a similar pattern, all suggesting that geroscience studies should go beyond investigating the speed of decline and also consider the possibility of improvements [6-8].

“Many people equate aging with an inevitable and continuous loss of physical and cognitive abilities,” said Levy. “What we found is that improvement in later life is not rare, it’s common, and it should be included in our understanding of the aging process.”

“Our findings suggest there is often a reserve capacity for improvement in later life,” she said. “And because age beliefs are modifiable, this opens the door to interventions at both the individual and societal level.”

Literature

[1] Levy, B. R., & Slade, M. D. (2026). Aging Redefined: Cognitive and Physical Improvement with Positive Age Beliefs. Geriatrics, 11(2), 28.

[2] Mehegan, L., & Rainville, C. (2023). ADULTS’ UNDERSTANDING OF COGNITIVE DECLINE, DEMENTIA, AND ALZHEIMER’S DISEASE. Innovation in Aging, 7(Suppl 1), 130.

[3] World Health Organization. (2004). Integrated Care for Older People (ICOPE): Guidance for Person-Assessment and Pathways in Primary Care; World Health Organization: Geneva, Switzerland

[4] Levy, B. R., Ferrucci, L., Zonderman, A. B., Slade, M. D., Troncoso, J., & Resnick, S. M. (2016). A culture-brain link: Negative age stereotypes predict Alzheimer’s disease biomarkers. Psychology and aging, 31(1), 82–88.

[5] Levy B. (2009). Stereotype Embodiment: A Psychosocial Approach to Aging. Current directions in psychological science, 18(6), 332–336.

[6] Levy, B. R., Pilver, C., Chung, P. H., & Slade, M. D. (2014). Subliminal Strengthening: Improving Older Individuals’ Physical Function Over Time With an Implicit-Age-Stereotype Intervention: Improving Older Individuals’ Physical Function Over Time With an Implicit-Age-Stereotype Intervention. Psychological Science, 25(12), 2127-2135.

[7] Meisner B. A. (2012). A meta-analysis of positive and negative age stereotype priming effects on behavior among older adults. The journals of gerontology. Series B, Psychological sciences and social sciences, 67(1), 13–17.

[8] Westerhof, G. J., Nehrkorn-Bailey, A. M., Tseng, H.-Y., Brothers, A., Siebert, J. S., Wurm, S., Wahl, H.-W., & Diehl, M. (2023). Longitudinal effects of subjective aging on health and longevity: An updated meta-analysis. Psychology and Aging, 38(3), 147–166.