LongeCityNews Last Updated: 18 March 2026 - 01:45 PM

Autophagy is the name given to a collection of cellular processes responsible for recycling damaged or otherwise unwanted proteins and structures. The materials to be recycled are conveyed to a lysosome where they are broken down into raw materials that can be reused for further protein synthesis. Many of the most well studied approaches to slowing aging in laboratory species involve increased autophagy. Greater autophagy improves cell function and is demonstrated to reduce the pace at which cells in aged tissues enter the harmful senescent state. Nothing in biology is simple, however. Here, researchers discuss the role of excessive autophagy in sustaining the inflammatory, disruptive signaling that is generated by lingering senescent cells in aged tissues.

Autophagy and cellular senescence are fundamental stress-response programs that critically shape aging and disease progression, yet their functional relationship has remained paradoxical. Autophagy is traditionally viewed as a cytoprotective process that preserves cellular homeostasis and delays senescence. In contrast, emerging evidence demonstrates that autophagy is also indispensable for the survival and pathological activity of established senescent cells. In this review, we propose a "threshold model" to reconcile these opposing roles and to provide a unified framework linking signal transduction, organelle quality control, and therapeutic intervention.

According to the threshold model, autophagy exerts stage-dependent functions governed by stress intensity and disease progression. Below a critical damage threshold, robust autophagic flux suppresses senescence initiation by maintaining mitochondrial integrity, limiting oxidative stress, and preserving proteostasis. Once this threshold is exceeded, autophagy is functionally reprogrammed to sustain the metabolic and biosynthetic demands of senescent cells, including production of the senescence-associated secretory phenotype (SASP).

We highlight key signaling nodes that regulate this transition, including mTORC1, AMPK, p53, and p62, as well as spatial and organelle-specific mechanisms such as the TOR-autophagy spatial coupling compartment (TASCC), mitophagy failure, lipophagy blockade, and aberrant nucleophagy. These processes converge on innate immune pathways, notably cGAS-STING and NF-κB signaling, to drive chronic inflammation and tissue dysfunction. Importantly, we extend this mechanistic framework to clinical translation, synthesizing evidence from ongoing trials in cancer, neurodegeneration, metabolic liver disease, and fibrosis. We argue that effective targeting of the autophagy-senescence axis requires precision gerontology, integrating dynamic biomarkers to guide stage-specific interventions-autophagy activation for prevention and autophagy inhibition or senolysis for established disease.

Link: https://doi.org/10.1016/j.redox.2026.104079

As researchers continue to map the changing composition of the gut microbiome in aging and disease, in ever more detail, they increasingly uncover the problematic activities of specific microbial species and specific mechanisms by which the aging of the gut microbiome can contribute to age-related loss of function throughout the body. This opens the door to the development of means of targeted adjustment of the gut microbiome's composition, and also to the development of therapies that interfere in specific interactions between the microbiome and tissues that cause issues.

Ageing is accompanied by declining memory function, with extremely heterogeneous manifestation in the human population. Brain-extrinsic factors influencing cognitive decline, such as gastrointestinal signals, have emerged as attractive targets for peripheral interventions, but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which inhibition of gut-brain signalling during ageing results in impaired neuronal activation in the hippocampus and loss of memory encoding.

Specifically, accumulation of gut bacteria that produce medium-chain fatty acids, such as Parabacteroides goldsteinii, can drive peripheral myeloid cell inflammation through GPR84 signalling. As a result, the function of vagal afferent neurons is impaired, the interoceptive signal received by the brain is weakened and hippocampal function declines. We leverage this pathway to define interventions that enhance memory in aged mice, such as phage targeting of Parabacteroides, GPR84 inhibition and restoration of vagal activity. These findings indicate a key role for interoceptive dysfunction in brain ageing and suggest that interoceptomimetics that stimulate gut-brain communication may counteract age-associated cognitive decline.

Link: https://doi.org/10.1038/s41586-026-10191-6

The gut microbiome changes with age in ways that negatively affect tissue function and health. This is known because we live in an age in which it costs little to accurately measure the composition of the gut microbiome from a stool sample: which microbial species, and the relative abundance of each species. Bacterial species can be distinguished from one another by differing sequences of the 16S rRNA gene, so low-cost and relatively unsophisticated gene sequencing approaches can be used to characterize an individual's gut microbiome. The result is something of a golden age in the identification of new ways to adjust the gut microbiome to improve health.

Today's open access paper stands out as interesting, in that the authors establish a correlation between the prevalence of a single bacterial species, Roseburia inulinivorans, and muscle strength in mice and humans. The Roseburia inulinivorans population diminishes with age. Increasing the Roseburia inulinivorans population size via supplementation with live bacteria enhances muscle strength in mice. The size of that increase in strength was on the order of 30%, more than large enough to expect the emergence of a deluge of Roseburia inulinivorans live probiotic supplements in the years ahead. A trial of those supplements will be needed to determine the size of the effect on human muscle strength, but given the low cost of single species probiotic manufacture, that seems worth the effort.

Roseburia inulinivorans increases muscle strength

Gut bacteria have been implicated in a wide range of health conditions, yet their potential role in preventing and treating muscle-wasting disorders remains largely unexplored. We aimed to investigate whether specific gut microbial species are associated with muscle strength and to explore underlying mechanisms linking the gut microbiota to muscle health. We conducted metagenomic analyses in cohorts of younger and older adults extensively phenotyped for muscle strength. Associations were tested between bacterial taxa and performance measures. Causality was assessed by oral supplementation of candidate species in antibiotic-treated mice. Metabolomic profiling and muscle phenotyping were performed to elucidate mechanisms.

The relative abundance of Roseburia inulinivorans, but not other Roseburia species, was positively associated with multiple strength measures including handgrip, leg press, and bench press in humans. Supplementation of R. inulinivorans in mice significantly enhanced forelimb grip strength, whereas other Roseburia species had no effect. Metabolomic analyses revealed that R. inulinivorans reduced amino acid concentrations in the caecum and plasma, while activating the purine and pentose phosphate pathway in muscle. These changes coincided with increased muscle fibre size and a shift from type I to type II fibres. Accordingly, we observed that the relative abundance of R. inulinivorans is lower in older adults compared with young adults.

R. inulinivorans emerges as a species-specific modulator of muscle strength, linking gut microbiota to muscle metabolism and function. These findings support its potential as a probiotic candidate for nutraceutical interventions targeting age-related muscle-wasting diseases.

Scientists have found a positive correlation between the abundance of the bacterium Roseburia inulinivorans in the gut and muscle strength in mice and humans, although the mechanism behind it is still unclear [1].

Can bacteria mimic exercise?

As we age, we lose muscle mass and strength. This decline is a major driver of frailty, disability, and poor health outcomes in older adults [2]. Exercise and nutrition are the best-known countermeasures, but they have limits, especially in people who are too frail or ill to exercise effectively. This is why researchers are on a hunt for exercise mimetics, therapies that recapitulate some benefits of exercise without the need to actually flex muscles. The need for such therapies has only grown after the introduction of Ozempic and other GLP-1 receptor agonists, which have been shown to cause a concerning lean mass loss alongside weight loss [3].

Over the past decade, researchers have discovered that the gut microbiome does far more than help digest food. It produces a myriad of molecules that influence metabolism, inflammation, and tissue function throughout the body, including muscle. However, no specific bacterial species had been causally linked to muscle strength in humans or animals.

The one bug that could

To bridge this crucial gap, scientists from the University of Almería and the University of Granada, together with researchers from Leiden University Medical Center (LUMC, Netherlands), started by taking stool samples from two human cohorts of 33 older adults and 90 young adults. The samples were analyzed and bacterial DNA sequenced. Microbiome composition was then cross-referenced with two metrics of physical performance: handgrip strength and maximal oxygen consumption during exercise (VO₂ peak), which measures cardiorespiratory fitness.

The researchers focused on the genus Roseburia, which initially showed positive associations with muscle-related outcomes. They then drilled down to the species level, comparing three Roseburia species: R. inulinivorans, R. faecis, and R. intestinalis. In older adults, those who had detectable R. inulinivorans in their stool showed 29% higher handgrip strength compared to those without it, with no corresponding difference in VO₂ peak. The other two species showed no significant association with handgrip strength.

In young adults, higher R. inulinivorans abundance was positively associated with both handgrip strength and VO₂ peak. R. inulinivorans and R. intestinalis also correlated with leg press and bench press strength. Importantly, the authors found no significant correlation between Roseburia abundance and dietary intake (energy, carbohydrate, fat, protein, or fiber), reducing the likelihood that diet was a confounder.

To move from correlation to causation, the authors gave live Roseburia bacteria to mice and measured whether it changed muscle strength. Thirty-two male mice (6 weeks old) were first treated with a broad-spectrum antibiotic cocktail for 2 weeks to deplete their native gut bacteria. Mice were then randomized into four groups (eight mice in each): vehicle control, R. faecis, R. intestinalis, or R. inulinivorans, delivered three times per week for 8 weeks.

None of the Roseburia species improved running time to exhaustion (an endurance/cardiorespiratory measure). However, R. inulinivorans produced a remarkable 30% increase in forelimb grip strength. This effect persisted even after correcting for lean body mass, meaning it was not simply because the mice were bigger. Mice receiving R. inulinivorans also had a larger muscle fiber cross-sectional area (CSA) compared to controls.

Interestingly, R. inulinivorans treatment shifted the soleus muscle toward a higher proportion of type II (fast-twitch) fibers relative to type I (slow-twitch) fibers. Type II fibers are associated with power and strength output, while type I fibers are more endurance-oriented. This finding squared well with the results obtained in the human cohort (increased muscle strength but not endurance).

Going after the mechanism

Since Roseburia species are well-known producers of butyrate, a short-chain fatty acid (SCFA) that has anti-inflammatory and metabolic signaling roles, the obvious hypothesis was that R. inulinivorans was boosting butyrate levels. The authors measured SCFAs in the cecal content and found no significant differences across the groups; butyrate was not the answer.

They then profiled amino acids and found that mice treated with R. inulinivorans showed the most dramatic shifts: cecal levels of methionine, leucine, isoleucine, alanine, valine, and lysine were all markedly reduced compared to controls. This looked like a paradox: why would a decrease in amino acid abundance lead to an increase in muscle strength?

Further experiments, which included a broad sweep of all detectable small molecules (untargeted metabolomics) on plasma and skeletal muscle from the mice, revealed that R. inulinivorans was associated with a much more pronounced shift in metabolites than other Roseburia species, including in those related to purine metabolism. Purines form the building blocks of DNA/RNA and are crucial for energy (ATP) and metabolism.

While the team clearly documented the metabolic changes, the full mechanism connecting them remains hypothetical. Roughly, when R. inulinivorans depletes amino acids in the gut, the host may compensate by prioritizing amino acid allocation to metabolically important tissues like muscle. Meanwhile, the muscle activates purine pathways to support nucleotide production and energy supply under amino acid-limited conditions, essentially becoming more effective. More research is needed to confirm this intriguing hypothesis.

Finally, the authors compared R. inulinivorans abundance between age groups. In their own cohorts, older adults (65+) had significantly lower R. inulinivorans than young adults (18-25). To validate this, they analyzed a dataset of 3,512 fecal metagenomes from healthy individuals. In that dataset, adults (18-65) had slightly higher R. inulinivorans than older adults, with no significant differences for the other two species. On the other hand, a meta-analysis incorporating all publicly available cohorts did not reach statistical significance for any Roseburia species, though the effect size for R. inulinivorans trended negative.

“Taken together, our findings provide solid evidence confirming the existence of a gut-muscle axis in which this identified bacterium positively modulates muscle metabolism and muscle strength,” said Jonatan Ruiz, professor in the Department of Physical Education and Sport at the UGR and researcher at the Joint University Institute for Sport and Health (iMUDS).

Literature

[1] Martinez-Tellez, B., Schönke, M., Kovynev, A., Garcia-Dominguez, E., Ortiz-Alvarez, L., Verhoeven, A., … & Rensen, P. C. (2026). Roseburia inulinivorans increases muscle strength. Gut.

[2] Cruz-Jentoft, A. J., Bahat, G., Bauer, J., Boirie, Y., Bruyère, O., Cederholm, T., … & Zamboni, M. (2019). Sarcopenia: revised European consensus on definition and diagnosis. Age and ageing, 48(1), 16-31.

[3] Wilding, J. P., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., … & Kushner, R. F. (2021). Once-weekly semaglutide in adults with overweight or obesity New England Journal of Medicine, 384(11), 989-1002.