Fight Aging!

Partial cell reprogramming as a basis for rejuvenation therapies is an area of great interest in the research and development communities. It has received greater funding in recent years than any other part of the field, with the founding of Altos Labs and a number of other unusually well-funded biotech companies. Reprogramming involves expression of some or all of the Yamanaka factors. Full reprogramming of a somatic cell slowly transforms that cell into a pluripotent stem cell, a recreation of the process of early embryonic development. Partial reprogramming for a shorter period of time only restores youthful epigenetic patterns of gene expression without changing cell state, and this, if it can be made to work in a living organism, is the basis for potential rejuvenation therapies.

The challenges of partial reprogramming, at least until people find a viable small molecule approach that seems safe enough to develop as a therapy, are the challenges of gene therapy, which is to say near entirely a matter of how to deliver the therapy in way that sufficiently controls degree and duration of gene expression. A given tissue can be made up of many different cell types that all need different approaches to partial reprogramming. Current gene therapy vectors struggle with effective delivery to many tissue types. Control over location and duration of expression is thus a major area of innovation in the field, a problem to be solved piece by piece. Today's open access paper is an interesting example of a novel approach to induced expression of a gene therapy, in that the induction occurs via pulsed electromagnetic fields rather than use of small molecules.

Scientists Prolong the Life of Mice With Invisible Energy Fields, New Study Shows

Researchers have established a method for inducing cellular reprogramming with electromagnetic fields (EMFs). Complete cellular reprogramming can cause cancer and early mortality, so the researchers implemented cyclic cellular reprogramming. To do so, they genetically engineered aged mice to activate cellular reprogramming genes in response to EMFs. They applied the EMFs cyclically to induce cyclic cellular reprogramming. The researchers then assessed the survival of the mice up until they were 108-weeks-old, which is roughly equivalent to the human age of 70.

The researchers found that over 75% of the reprogrammed mice lived to 108-weeks-old. Only about 60% of untreated mice survived until 108-weeks-old. To be thorough, the researchers also monitored normal-aged mice that were not genetically engineered. The survival rate for these mice was even lower, at about 50%. These findings suggest that EMF-induced cyclic cellular reprogramming can prolong the lifespan of aged mice. The researchers also found that EMF treatment countered certain aspects of aging in the engineered mice. The aorta, which thickens with age, was restored to normal thickness. Additionally, the treatment improved skin thickness and liver cell numbers, which decline with age, and it rejuvenated the spleen and kidneys. There were also signs of reduced senescent cells, which are cells that can accumulate with age and promote inflammation and tissue damage. The mice also become visibly younger, with less of a hunched back, better grooming, and a reduction in gray hair.

They started by asking a simple question: which genes naturally respond to EMFs? In mouse brain tissue, they identified one gene in particular - called Lgr4 - that could be activated and deactivated quickly. They then focused on the gene's promoter, a stretch of DNA that modulates when a gene turns on or off. From this region, they chose a specific sequence and named it Ei, short for "EMF-inducible DNA element." However, this did not explain how the EMFs actually trigger this switch. To find out, the researchers looked at what was happening inside cells. Their experiments suggested that EMFs interact with a protein called Cyb5b, setting off a chain reaction that releases calcium ions (Ca2+). Remarkably, the released Ca2+ oscillated at a frequency that activates the Ei switch.

Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression

Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The EMF-inducible gene switch was activated by rhythmic oscillatory calcium dynamics rather than generic calcium influx, defining a precisely tuned and bio-orthogonal induction mechanism.

Functionally, EMF activation of the Oct4-Sox2-Klf4 (OSK) cassette induced in vivo partial reprogramming in aged mice, conditional expression of human mutant amyloid precursor protein (APP) for Alzheimer's disease (AD) modeling recapitulated pathological features, and EMF-mediated Tph2 expression restored serotonergic activity and ameliorated depressive-like behaviors in Tph2-mutant depression mice. Overall, a remotely controlled EMF-inducible gene switch represents a versatile and effective biomedical platform.

Our perception of the passage of past time appears to change with age. Studies suggest that when looking back at recent personal history in later life time appears to have passed more rapidly than it did in youth. One potential explanation for this is that people recall less of what happened in later life than they do in earlier life, or that the storage or retrieval of experiential memory becomes otherwise more compressed. Studies of recall suggest that we remember something like 2% of our experience; we're all ghosts of ourselves in that sense. Does this tiny fraction become even smaller with advancing age, and if so, why does this occur? The author of this paper offers a testable hypothesis connected to age-related declines in energy metabolism in the brain.

A year of chronological time is typically assumed to represent comparable experiential encoding across individuals and age groups. This assumption is rarely examined. Yet subjective reports across adulthood consistently suggest that extended periods - months and years - are often remembered as having "passed quickly," particularly in later life. Importantly, this phenomenon does not imply a change in objective time but reflects differences in how time is encoded and reconstructed. Time-perception research distinguishes moment-to-moment passage-of-time judgments from retrospective duration judgments, and evidence indicates that long-interval judgments rely heavily on memory structure rather than internal clock mechanisms.

I introduce the concept of experienced longevity, defined as the amount of lived time subjectively contained within a fixed chronological interval. Within the present framework, this construct is operationalized through experiential density, defined as the number and distinctiveness of event units segmented, encoded, and later retrievable per unit of chronological time. I propose that age-related biological changes - particularly declines in mitochondrial efficiency, increased vascular stiffness, and reduced nitric oxide-mediated neurovascular coupling - may constrain the brain's capacity for high-fidelity updating during ongoing experience. By limiting event segmentation and episodic distinctiveness, these neuroenergetic constraints may increase the probability of retrospective temporal compression.

I term this framework the Neuroenergetic Constraint Model of experienced longevity. In this framework, experienced longevity is the broader aging-related construct, experiential density is the proximate memory-level property through which it is expressed, and retrospective temporal compression is the downstream subjective outcome expected when that density is reduced.

Link: https://doi.org/10.3389/fnagi.2026.1815030

Greenland sharks can live for at least a few centuries, and are thus of interest in the study of the comparative biology of aging. Here, researchers take a first step in examining the cellular biochemistry of aging in this species. As a rule, aquatic species are less well investigated in this regard than is the case for land animals, and most land animals are less well investigated than mammals. One never knows what might be discovered, of course, though it remains the case that efforts to bring beneficial mechanisms from a long-lived species into a short-lived species are in their infancy. Developing therapies based on the biochemistry of a long-lived species has yet to happen, so it is hard to predict just how great a utility this research will provide over time.

The Greenland shark (Somniosus microcephalus), with a lifespan estimated around 300 years, represents a unique model for studying vertebrate longevity. Here, we characterize its cardiac aging profile and compare it with two other species: the deep-sea shark Etmopterus spinax and the short-lived teleost Nothobranchius furzeri.

Histological analysis revealed extensive interstitial and perivascular fibrosis throughout the ventricular myocardium of S. microcephalus, affecting both compact and spongy layers of both sexes. This fibrotic pattern was absent in E. spinax and N. furzeri, suggesting it is a specific feature of S. microcephalus. We also observed extreme lipofuscin accumulation within cardiomyocytes of S. microcephalus, which correlates at the ultrastructural level with the abundance of damaged mitochondria and the presence of strikingly enlarged lysosomes filled with electron-dense material of likely mitochondrial origin. Additionally, in the myocardium of S. microcephalus we found abundant deposition of the oxidative stress marker 3-nitrotyrosine.

Remarkably, despite showing multiple canonical markers of aging such as fibrosis, lipofuscin accumulation, and oxidative stress, S. microcephalus individuals appeared healthy and physiologically uncompromised at the time of capture. These findings suggest that S. microcephalus has evolved resilience to molecular and tissue-level aging signs and hallmarks, supporting sustained cardiac function over centuries and offering new insights into the mechanisms of extreme vertebrate longevity.

Link: https://doi.org/10.1111/acel.70505

The immune system becomes dysfunctional with age. On the one hand it becomes overly active and inflammatory, a state known as inflammaging. Many of the forms of cell and tissue damage characteristic of aging can provoke the immune system into an inflammatory response. One example is the increasingly well studied mislocalization of mitochondrial DNA and nuclear DNA fragments within the cell. This mislocalized DNA triggers sensors that evolved to detect viruses and bacteria, leading to cells alerting the immune system with inflammatory signaling. When that mislocalized DNA is a constant feature of a sizable population of dysfunctional cells, the consequent inflammatory signaling never ceases. Chronic unresolved inflammation alters cell behavior for the worse, and is damaging to tissue structure and function.

While constantly on alert, the aged immune system also becomes less capable, the state known as immunosenescence. It falters in its vital tasks of defense against infectious pathogens, maintenance of tissues, and destruction of senescent and potentially cancerous cells. The immune system becomes increasing populated by exhausted, senescent, and malfunctioning immune cells. In the brain, specialized populations of immune cells such as microglia are vital to the ongoing function, maintenance, and change of synaptic connections between neurons, and these tasks are also impaired by immune aging. Thus the complex aging of the immune system contributes to the onset and progression of neurodegeneration in a range of ways beyond the obvious issues of chronic inflammation and incapacity, as researchers note in today's open access paper.

Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications

mmunosenescence, together with chronic low-grade inflammation known as inflammaging, reflects the age-associated decline in immune competence, characterized by coordinated functional, structural, and metabolic alterations rather than a sudden failure. These changes include remodeling of lymphoid tissues, shifts in immune cell composition and dysregulation of immune responses, ultimately reducing the ability to respond to novel pathogens. As a consequence, older adults are more susceptible to infections, autoimmunity, cancer and neurodegenerative diseases (NDDs). NDDs represent a major challenge of population aging due to their rising prevalence, inter-individual variability and the lack of disease-modifying therapies. These disorders are characterized by the gradual loss of neurons, which progressively impairs motor, sensory, and cognitive functions.

Growing evidence suggests that immunosenescence and inflammaging are not merely secondary consequences of neurodegeneration but actively contribute to disease susceptibility, progression and therapeutic resistance. Systemic immune aging and immune dysfunction within the central nervous system (CNS) converge to establish a persistent pro-inflammatory milieu that may disrupt neuronal homeostasis and contribute to neurodegeneration. Emerging data also indicate that age-related alterations in peripheral immunity can influence neuroimmune crosstalk and may modulate disease onset and progression.

Despite compelling evidence that immune aging is a key driver of neurodegenerative diseases, several conceptual and translational challenges remain. A major limitation is the lack of validated, disease-relevant biomarkers that reliably capture immunosenescence and inflammaging in humans. Immune aging is a multidimensional process encompassing cellular senescence, altered immune repertoire diversity, metabolic dysfunction and chronic inflammatory signaling, yet most clinical studies rely on isolated markers or systemic inflammatory readouts.

Another critical challenge lies in bridging mechanistic insights from basic immunology and neurobiology with clinical trial design. Preclinical models have convincingly demonstrated that immunosenescence and inflammaging actively shape glial dysfunction, blood-brain barrier integrity, and neuronal vulnerability. However, most clinical interventions are initiated at symptomatic stages, long after immune-driven neuroinflammatory loops are established. This temporal mismatch likely contributes to the limited efficacy of immune-modulating and senescence-targeting therapies in human neurodegenerative diseases. Translational strategies must therefore prioritize early intervention windows, stratification of patients by immune-aging phenotypes, and a clearer distinction between systemic and CNS-compartment-specific immune dysfunction.

Glycation arises from the interaction of sugars with proteins, decorating proteins with additional structures that alter their function. Advanced glycation endproducts (AGEs) are a broad class of glycated proteins. The presence of AGEs is a form of stress on cells and systems in the body; some forms drive chronic inflammation through interaction with the receptor for AGEs (RAGE), while other forms alter the structural properties of the extracellular matrix by cross-linking collagen and other molecules to restrict their motion. Relatively little work has taken place on ways to address the problem of excessive AGEs in aging and age-related disease, unfortunately. Compared to more popular topics in the life sciences, the study of AGEs, and particularly their interactions with the extracellular matrix, remains underfunded and gives rise to little in the way of efforts to produce therapies to tackle this aspect of aging.

Biological molecules seldom act alone. Within the crowded environment of a cell, proteins, lipids, and nucleic acids are constantly surrounded by sugars and metabolites that test their stability and shape. Among these interactions, glycation stands out as a subtle yet far-reaching reaction, linking the routine chemistry of metabolism to the gradual story of molecular aging. Often described as the Maillard reaction, glycation is a spontaneous nonenzymatic process in which simple sugars or their reactive derivatives attach covalently to amino acid residues such as lysine, arginine, and cysteine. The resulting adducts evolve into Amadori compounds and eventually into advanced glycation end products (AGEs), which alter protein conformation, solubility, and biological activity.

In living systems, glycation proceeds slowly but accelerates with age, becoming a hallmark of molecular aging. Beyond structural damage, AGEs act as signaling molecules by binding to the receptor for advanced glycation end products (RAGE). This interaction triggers oxidative stress, inflammation, and tissue remodeling that contribute to chronic disease. Clinically, glycation serves as both a biomarker and a therapeutic target. Measurements such as glycated hemoglobin and glycated albumin provide indicators of metabolic control, while pharmacological and nutritional strategies aim to limit AGE formation, disrupt crosslinks, or block receptor-mediated signaling

This review synthesizes the molecular pathways of AGE formation, their structural diversity, and the biological factors influencing glycation kinetics. Advances in analytical detection methods - including fluorescence spectroscopy, LC-MS/MS, and immunochemical approaches - are highlighted for their role in monitoring AGE accumulation. Particular attention is given to the contribution of glycation to diabetes, cardiovascular disease, neurodegeneration, and cancer, alongside emerging therapeutic strategies to limit AGE formation or block AGE-RAGE signaling. Glycation thus represents a central mechanism in human disease pathogenesis and an emerging therapeutic frontier.

Link: https://doi.org/10.3390/diseases14040137

Stem cells support tissues by generating a supply of daughter somatic cells to replace losses. A broad body of evidence points to reduced muscle stem cell activity as a major contributing cause of age-related loss of muscle mass and strength. Other evidence suggests that this stem cell population remains capable; when old muscle stem cells are removed from the aged tissue environment for assessment, they appear to be as capable as young muscle stem cells. Researchers are now interested in establishing how an aged environment interacts with muscle stem cells to reduce their activity, with an eye to developing therapies to interfere in specific mechanisms as they are uncovered.

Frailty arising from loss of muscle function and mass is a significant health concern impacting quality of life and dramatically increasing health care costs as our population ages. Ameliorating frailty derived from reduced muscle function is thus a critical research priority to improve health span. Cell intrinsic defects in muscle stem cells (MuSC), or satellite cells, occur as skeletal muscle ages, reducing the capacity of MuSCs to maintain and repair skeletal muscle and are accompanied by cell nonautonomous changes.

Although rejuvenating stem cells in aged tissues or organs has potential to improve muscle aging phenotypes, we found that the extracellular environment in aged mice abrogates rejuvenated muscle stem cell potential. MuSCs from young mice were unable to grow on extracellular matrix derived from aged mice that contains elevated collagen protein levels, establishing a critical role for the environment in contributing to muscle phenotypes in aging. Combining an inducible FGF receptor 1 (FGFR1) to rescue MuSC intrinsic aging defects with a drug to reduce fibrosis partially rescued muscle mass loss in aged mice. We conclude that aging affects tissues, and particularly skeletal muscle tissue, via complex multifactorial processes requiring multifaceted interventions to improve aging phenotypes.

Link: https://doi.org/10.64898/2026.04.10.717808

The collective influence on aging of insulin, insulin-like growth factor (IGF-1), growth hormone, and the receptors for these signal molecules is well studied. It is arguably the most well studied area of cellular biochemistry and metabolism in the context of aging, a central set of mechanisms that regulate the evolved trade-off between growth and maintenance, and which is strongly influenced by the equally well studied intervention of calorie restriction. Numerous animal studies have demonstrated that interfering in various specific parts of this collection of signaling processes is capable of at least modestly slowing aging. In the case of the growth hormone receptor, genetic engineering to cause life-long loss of function produced what remain the longest lived mouse lineages to be generated in the laboratory. These dwarf mice live up to 70% longer than unmodified peers.

Humans with Laron syndrome exhibit essentially the same loss of function and dwarfism, but while they may prove to be more resistant to some age-related diseases, they unfortunately do not exhibit a sizable increase in life span. The same is true for the practice of calorie restriction; humans may gain a few years, but clearly not the 40% extension of life span that has been observed in mouse studies. The evolution of mechanisms relating to growth, maintenance, and availability of food has led to a great plasticity of life span in short-lived species, but not in long-lived species. The health benefits resulting from the practice of calorie restriction in humans are considerable relative to what can be achieved using near all existing forms of medicine, but fall far short of our aspirations for the future.

Nonetheless, the development of calorie restriction mimetic drugs is a major focus in the research and development communities, an attempt to indirectly interfere in the regulation of growth versus maintenance by provoking some of the same reactions as take place in an environment of a reduced calorie intake. Another area of interest is the development of drugs that interfere more directly with the IGF-1 signaling involved in regulating growth versus maintenance. Today's open access paper is an example of a proof of concept study aimed at inhibition of the IGF-1 receptor, using drug candidates that would not be suitable for further development due to their side-effect profiles. They nonetheless produce a modest slowing of aging in mice.

Small-molecule IGF1R inhibitors extend healthspan in a mouse model

Antagonistic pleiotropy of the IGF-1 signaling cascade is well recognized, as it promotes growth and development at younger ages and delays aging later in life. The goal of this study is to test in a mouse longevity experiment whether orally delivered small-molecule IGF1R inhibitors have promise as an anti-aging therapy. C57BL/6 mice (25 male and 25 female mice per treatment) were treated with selective IGF1R inhibitors, picropodophyllin (PPP) or 5-[3-(phenylmethoxy)phenyl]-7-[trans-3-(1-pyrrolidinylmethyl)cyclobutyl]-7H-pyrrolo[3-d]pyrimidin-4-amine (NVP-ADW742), via powdered diets starting at 13 months of age, and physiological and behavioral parameters, as well as survival, were assessed.

Both compounds protected both sexes from short-term memory decline; reduced systolic blood pressure in males and pulse rate in both sexes; rescued declining glucose tolerance in males; and abolished grey hair development, reduced frailty, and protected against decline in grip strength in female mice. There were no sex differences in survival curves within groups. No significant differences between groups were observed in the Kaplan-Meier analysis of survival. However, the survival curve in the NVP-ADW742 group was "squarer" than in controls, indicating a 93-day longer healthspan. PPP treatment was associated with toxicity (gastrointestinal bleeding). Additional analysis of the drug likeness of NVP-ADW742 demonstrated potential cardiotoxicity and brain bioaccumulation.

To conclude, small-molecule IGF1R inhibitors hold promise as a therapy that may improve human health span and lifespan; however, both molecules tested in this study have side effects that may outweigh their anti-aging effects.

Naked mole-rats live very much longer than other similarly sized rodents, and exhibit very little age-related decline until very late life. Researchers use this species as a point of comparison to attempt to better understand mechanisms of aging that might be targeted in mice and humans. Here, for example, the focus is on naked mole-rat skin structure. As is the case for other organs, old naked mole-rat skin doesn't exhibit the evident signs of aging observed in old mice and humans. Why is this the case? A first step is to catalog the structural and biochemical differences as best possible; given a reasonably comprehensive catalog, deeper investigations can then proceed.

Naked mole-rats are extremely long-lived rodents with a lifespan of up to 40 years, during which cellular and tissue aging is rarely observed. In this study, we analyzed the extracellular matrix (ECM) of naked mole-rat skin at the molecular level to elucidate the molecules involved in anti-aging and their localization. Raman spectroscopy and Fourier transform infrared spectroscopy were applied to investigate the hierarchical structure of the ECM, showing that, whereas the epidermis of aged mice had thinned, the epidermis of naked mole-rats became thickened and hyaluronic acid (HA) was distributed under the basement membrane. Furthermore, naked mole-rat skin had a regular skin texture and flexibility, allowing the maintenance of a youthful appearance.

Hyaluronic acid in naked mole-rats characteristically exists as clusters (chain HA) in skin tissue, where it is thought to permit moisture retention and maintain elasticity, contributing to the skin's youthful appearance. These results suggested that not only the density of ECM but also its spatial distribution and topographic properties are important for skin anti-aging. Our findings may contribute to the elucidation of skin disease pathology, the development of therapeutic gel scaffolds, and the control of aging.

Link: https://doi.org/10.3390/gels12040303

Long-lived naked mole-rats are eusocial: like ants and bees, they live in colonies led by a queen that is the only female that reproduces. Naked mole-rats are extremely long-lived in comparison to other similarly sized mammals, and this tendency towards greater longevity shows up in many other eusocial species. It crosses evolutionary clades and ecological niches, which might lead one to ask what exactly it is about eusociality that promotes longevity. Here, researchers offer a hypothesis based on modeling.

Animals such as bees, ants, wasps, termites, and naked mole-rats live in colonies in which a single queen is the only female reproductive, an arrangement known as eusociality. Eusocial animals are known for their remarkably long lifespans. It has been argued that longevity becomes selected when queens are shielded from "external mortality". While such protection may contribute, we find a deeper reason: the eusocial reproduction strategy itself inherently creates selection for long lifespans.

Lifespans typically reflect two processes: the baseline risk of death and the rate at which this risk increases with age. Each is a parameter in the Gompertz mortality equation. We show that the mathematical properties of eusocial reproduction lead to slowly-growing, older populations where selection acts more strongly on the rate at which risk increases than on the baseline risk. In addition, we show that channeling reproduction through a single female also selects for longevity, which we term the "queen effect". Thus, the dynamics of eusocial reproduction select for longer lifespan. More broadly, these results show that reproductive structure and population growth dynamics can fundamentally shape selection on lifespan, with implications outside eusocial systems as well.

Link: https://doi.org/10.1101/2025.03.25.645350

The article that I'll point out today is primarily intended to explain to a layperson the recent history of partial reprogramming as an approach to the treatment of aging and age-related disease. The article clearly exists because the leadership at Altos Labs wants to attain a higher profile in the public eye. Altos was created in 2022 or thereabouts and funded with the immense sum of $3 billion, a sizable fraction of all biotech investment in that year. Thus the usual reason for increased publicity, meaning the desire to raise further funding from investors, seems less likely.

It is perhaps the case that there is some pressure behind the scenes to show results, particularly now that Life Biosciences has commenced a first human trial of a very narrowly focused use of partial reprogramming for optic nerve injury or degeneration. Biotech is a slow business, however, in which fifteen years between initial research and clinical approval is entirely normal. Nonetheless, one might imagine that more knowledgeable types might look back at the history of the Ellison Medical Foundation and Calico Life Sciences and express some concern that perhaps large amounts are once again being spent to, as yet, no evident good. This is of course all speculation, but we shall see.

Longevity Science Is Overhyped. But This Research Really Could Change Humanity

When a woman gets pregnant, she has been carrying her egg cells since birth. The sperm that joins with the egg to form a zygote might have been just a few months in the making, but it inherits markers of age from the man who produced it. It only follows that the zygote would also show signs of age - and at first it does. But then a mysterious metamorphosis begins: the cells of the zygote begin to reverse that damage, shaking off the metaphorical (epigenetic) dust that the parents accumulated on their DNA. After two weeks, the cells of the embryo are back to a kind of ground zero of youth. Recreating this rejuvenation is one of the newest and most promising developments in longevity research.

Over the past 20 years, they have learned how to trigger rejuvenation in the lab, achieving a series of breakthroughs that have made that future feel tantalizingly close. Scientists have taken skin cells from 90-year-olds and restored them to youth in a petri dish. They have rejuvenated diseased mice, turning their gray hair back to black and strengthening their muscles. Rejuvenation sounds just as sci-fi as any of the ideas coming out of the longevity field, and yet there's widespread agreement among scientists that the research has extraordinary potential. The most vehement disagreements are not over whether cellular aging can be reversed, but how far scientists can push it. Will it work in humans? Will its use be limited to targeted interventions that cure specific diseases? Or could it ever be safe enough to enable full-body rejuvenation - to help humans look and feel younger, or to stop them from aging in the first place?

Some of the answers to those questions are likely to come from Altos Labs, a secretive biotech company. With $3 billion in investment at its founding in 2022, Altos is thought to have been the single largest biotech start-up launch. A would-be Manhattan Project for longevity science, Altos is responsible for one of the biggest migrations of academics to industry in recent years, luring marquee names in the field with million-dollar salaries and the promise of near-unlimited funding. Among its competitors, Altos has earned a reputation as a black box.

In 2006, Shinya Yamanaka identified four unusual genes that are active in early embryonic development. He introduced them into the skin cells of older mice in a petri dish and watched and waited. Over the course of two weeks, the skin cells transformed, becoming something close to embryonic stem cells. The original Yamanaka factors are now considered just one of many potential ways that scientists could trigger rejuvenation. Altos and a handful of other start-up biotech companies are competing to find the safest version. Altos is conducting research on rejuvenation in the kidney, the heart, and the liver, which are often the first organs to fail as we age. The hope is that in fixing whatever organ is aging first, scientists could give someone a longer, healthier life, with everything essentially winding down at the same time, making for a mercifully brief period of decline.

Some varieties of hydra are immortal, in the sense that mortality rate and measures of function do not change over time. A hydra is in essence a sophisticated bundle of stem cells, somewhat analogous to an early embryo, capable of replacing any of its component parts. Are there aspects of hydra cellular biochemistry that could be introduced into more structured, sophisticated species to extend life? One view is that hydra-like strategies for longevity are incompatible with a central nervous system that retains information. Another view is that this point doesn't rule out all of the potentially interesting biochemistry in this species. Certainly, researchers have already started to move genes and other aspects of cellular biochemistry from long-lived species to short-lived species, such as from naked mole rats to mice, in order to test the bounds of the possible.

Hydra vulgaris ("Hydra") exhibits negligible senescence due to continuous self-renewal and stem cell cycling, contrasting sharply with short-lived, eutelic rotifers that exhibit rapid aging and fixed somatic cell numbers post-development. These organisms therefore represent extremes on the spectrum of invertebrate lifecycles and offer a unique opportunity to test whether patterns of gene expression associated with repressed senescence in Hydra can delay senescence in aging-prone animal models. We hypothesize that introducing Hydra-like gene expression profiles into rotifers (e.g., Brachionus manjavacas) via genetic manipulation will extend healthspan and reduce age-related mortality, providing proof-of-principle for effective manipulation of conserved anti-aging mechanisms.

While translation to humans remains highly speculative at this early stage, the rotifer-Hydra model provides a proof-of-principle framework for discovering targets potentially more relevant to mammalian aging than those from other invertebrate systems. If Brachionus manjavacas can, at least to some extent, exhibit more negligible senescence via transfer of relevant Hydra-like gene expression patterns, this would constitute the required proof-of-principle for the overall concept. It is a long leap from rotifers to geroprotective strategies for humans, but without the initial step from Hydra to rotifer, nothing else would likely be possible. Therefore, we posit that Hydra to rotifer, considered long term, is of relevance to the question of aging, senescence, and geroprotective strategies for humans.

Link: https://doi.org/10.18632/aging.206370

Lung fibrosis is challenging to treat and largely irreversible. There have been signs that clearance of senescent cells can improve the condition, but this has yet to move beyond early human safety trials. Here researchers take a more traditional approach to assessing and then tinkering with the expression of specific genes to produce a reduction in fibrosis in animal models. After finding that ID1 and ID3 exhibited elevated expression in some lung cells, they showed that reducing expression via a variety of means caused some degree of reversal of fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease in which scar tissue builds up in the lungs, making it increasingly difficult to breathe. Existing therapies can slow disease progression but do not stop or reverse it, and most patients survive only three to five years after diagnosis. The research combined analyses of human lung tissue and cells from patients with IPF with several experimental models in mice. The team found that ID1 and ID3 levels are elevated in diseased lung fibroblasts - cells that drive the formation of scar tissue.

When both proteins were inhibited, fibroblast activation was significantly reduced, limiting the processes that lead to pulmonary fibrosis. The researchers tested multiple strategies to block ID1 and ID3, including a small molecule drug and a targeted gene therapy approach. Across these approaches, inhibition of the proteins not only slowed disease progression but also reduced established pulmonary fibrosis in mice and improved lung function. The study also sheds light on how these proteins contribute to disease. ID1 and ID3 regulate fibroblast growth through cell cycle pathways and promote scarring through MEK/ERK signaling - key mechanisms underlying pulmonary fibrosis.

Link: https://www.eurekalert.org/news-releases/1125917

The blood industry is enormous, a long-standing component of the medical industry and one of the largest areas of focus for regulators. Blood is donated and sold in immense amounts, processed and separated into countless different fractions, and those fractions used in equally immense amounts. A sizable research and development community views the contents of human blood in much the same way as others view libraries of small molecules: a domain in which the focus is on discovery of potential new uses in medicine.

Since the modern resurrection of heterochronic parabiosis studies, in which an old mouse and young mouse have their circulatory systems linked, the role of alterations in blood contents with age has been a growing topic of interest. Evidence strongly suggests that old blood is harmful, while less robust evidence suggests that specific factors in young blood might be favorable. For example, one novel approach to therapy under development involves clearing circulating TGF-β while increasing circulating oxytocin, a little from both sides. There is, however, a great deal of ongoing research into many different approaches to improving health in old people by manipulating the circulating contents of the bloodstream.

Blood as the mirror and modulator of aging: mechanistic insights and rejuvenation strategies

Aging arises not only from intrinsic cellular decline but also from systemic alterations in circulating factors that govern tissue maintenance and regeneration. Recent multi-omics advances - including plasma proteomics, metabolomics, and single-cell immunomics - highlight blood as both a mirror and a modulator of organismal aging. Circulating proteins and metabolites reflect not only chronological and biological age but also organ-specific aging trajectories, serving as robust predictors of healthspan, longevity, and disease risk. Beyond their diagnostic value, blood-borne components actively dictate the tempo of aging by shaping immune remodeling, metabolic homeostasis, and interorgan communication.

Youthful circulation, defined as the blood-borne systemic environment of young individuals, promotes tissue homeostasis and regeneration and, when experimentally transferred via heterochronic parabiosis or young plasma transfer, induces transcriptomic, metabolic, and epigenetic rejuvenation across multiple tissues. Specific fractions - such as small extracellular vesicles, plasma proteins, and metabolites - restore mitochondrial function, suppress inflammation, and extend lifespan in animal models. Conversely, reducing pro-aging factors through plasma dilution or therapeutic plasma exchange mitigates age-associated decline and shows translational promise in neurodegenerative disease. Collectively, these insights position blood as a central regulatory axis of aging.

Human epidemiological data robustly indicates a trade-off between risk of cancer and risk of neurodegenerative conditions. Why is this the case? While all too little is understood of the precise details, at the high level it is thought that this is a reflection of the degree to which tissue maintenance activities decline with age. The less work undertaken by stem cells, the less cell replication in general, the lower the risk of a potentially cancerous combination of mutations occurring. But without that ongoing maintenance, the loss of tissue function accelerates, and neurodegenerative conditions are one of the more prominent outcomes. In essence one is forced to choose between cancer or regeneration. Not all species face that choice, of course. Some, like naked mole rats, can have their cake and eat it too; their cancer suppression mechanisms are so exceptionally effective that individuals can maintain youthful levels of regeneration and function well into late life without any downsides.

Neurodegeneration and cancer are fundamentally distinct disorders: one signifies gradual neuronal loss while the latter signifies uncontrolled cell growth and survival. However, emerging evidence explores an inverse association between these conditions, suggesting that they do not arise from independent biological processes. Understanding the context-dependent behaviour of major pathways (for example, p53, PI3K/AKT/mTOR, Wnt, and immune-stress signaling) remains pivotal in elucidating the relationship between these two diseases. Pathways promoting early-life fitness, tissue repair, and tumor suppression in dividing cells can become detrimental later in life for post-mitotic neurons.

Cross-species genomics studies reveal how evolution has repeatedly adapted these shared networks to balance cancer resistance with survival. Research on species exhibiting exceptional longevity and disease resistance, including naked mole rats and bowhead whales, shows that cancer resistance and longevity are not fixed traits but rather are controlled by precise regulatory mechanisms. In this review, we integrate insights from broad species genomics and multi-omic and single-cell studies to understand how evolutionarily conserved molecular crosstalks diverge at the interface of cancer and neurodegeneration.

Link: https://doi.org/10.3390/ijms27072989

Inflammation in the brain is thought to be important in the progression of neurodegenerative conditions, disruptive to cell and tissue function. Understanding why the other features of neurodegenerative disease activate chronic inflammation in the brain is a necessary first step on the long road to the development of therapies capable of selectively suppressing this harmful inflammation while only minimally interfering in the normal, necessary inflammatory response to pathogens and injury.

The protein called STING normally functions as part of the immune system's early-warning system. In the brains of people with Alzheimer's, the team discovered that STING undergoes a chemical modification known as S-nitrosylation (or SNO, a reaction involving sulfur, oxygen, and nitrogen) that promotes its overactivation. Blocking this chemical change to STING in a mouse model of the disease decreased neuroinflammation.

Over three decades ago researchers discovered the S-nitrosylation process, in which a molecule related to nitric oxide (NO) binds to a cysteine amino acid in proteins, producing "SNO" and thus regulates the protein's function. SNO, which can be triggered by aging, neuroinflammation, and environmental toxins such as air pollution and wildfire smoke, disrupts a variety of different proteins in the body.

In this new study, the team focused on the protein STING, which was previously linked to Alzheimer's inflammation. They pinpointed exactly where on STING an S-nitrosylation reaction occurred, homing in on one specific building block of the protein: cysteine 148. When cysteine 148 is S-nitrosylated, they discovered, STING clusters into larger complexes and triggers inflammation. The team found high levels of the chemically modified form of STING (called SNO-STING) in postmortem brain tissue from Alzheimer's patients, in human brain immune cells grown in the lab and exposed to Alzheimer's proteins, and in a mouse model of the disease.

In laboratory experiments, the team showed that the clumps of proteins found in the brain in Alzheimer's - including amyloid-beta and alpha-synuclein - can themselves trigger the S-nitrosylation reaction in STING. This finding suggests that inflammation occurs in a cycle: initial protein clumps, coupled with environmental influences and aging, could cause inflammation that generates NO, driving S-nitrosylation of STING, which in turn drives more inflammation.

The researchers then engineered a version of STING lacking cysteine 148 so it couldn't be S-nitrosylated. When this modified protein was introduced into a mouse model of Alzheimer's, brain immune cells showed significantly less inflammation, and critically, the connections between nerve cells (called synapses) were protected from degradation. This preservation of synapses is known to correlate with protection from the cognitive decline of dementia.

Link: https://www.scripps.edu/news-and-events/press-room/2026/20260423-lipton-alzheimers.html