Federica Grosso from the  Institute for Genetic and Biomedical Research (IRGB) of the National Research Council (CNR) in Monserrato, Italy, describes a #research paper she co-authored that was #published in Volume 17, Issue 8 of Aging-US, entitled “Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.”

DOI - https://doi.org/10.18632/aging.206293

Corresponding author - Serena Sanna - serena.sanna@cnr.it

Video interview - https://www.youtube.com/watch?v=qYg42_gn_pw

Abstract

In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms.

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Keywords - aging, causal inference, aging, gut microbiome, inflammatory proteins, age-related macular degeneration

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Aging-US

Behind the Study: Gut Microbiome Links to Age-Related Traits and ApoM Protein

In this episode of Aging For All, hosts Jen Yanez Pryor and Andrea Price welcome Glenis Boyd-Hughes, an intersectional gerontologist. Glenis shares her journey into gerontology, emphasizing the importance of understanding the social drivers of health and the impact of intersectionality on aging. The conversation explores how societal systems shape aging experiences and the need for community engagement and advocacy to create better outcomes for elders. Glenis encourages listeners to view aging as a gift and to take action in their communities to support others.

Redefining Aging: An Intersectional Approach with Glynis Boyd Hughes

Imagine you could write a letter to your younger self. What would you tell them?

A Letter To My Younger Self: Middle Age Renaissance Man

As life expectancy increases, there is growing interest not only in extending lifespan but also in improving the quality of those additional years. To address the physical and cognitive decline that often accompanies aging, researchers have explored a variety of strategies. Many of these focus on a single biological factor, such as reducing inflammation or stimulating stem cell activity. However, aging is a complex process involving multiple, interconnected changes in the body.

Recognizing this, researchers at the University of California, Berkeley proposed a more comprehensive approach: targeting multiple aging-related pathways simultaneously. Their study, titled “Sex-specific longitudinal reversal of aging in old frail mice,” was recently featured on the cover of Aging-US (Volume 17, Issue 9).

Full blog - https://aging-us.org/2025/10/new-anti-aging-combo-boosts-lifespan-in-old-male-mice/

Paper DOI - https://doi.org/10.18632/aging.206304

Corresponding author - Irina M. Conboy - irina@generationlab.co

Abstract video - https://www.youtube.com/watch?v=bpWxDd7hHhM

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Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences

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New Anti-Aging Combo Boosts Lifespan in Old Male Mice

BUFFALO, NY — October 3, 2025 — A new #research perspective was #published in Volume 17, Issue 9 of Aging-US on August 26, 2025, titled “Analysis of the current state of frailty indexes and their implementation for aging intervention studies.” 

In this work, led by first author Oliver G. Frost from  Loughborough University alongside corresponding authors Abdelhadi Rebbaa and Amit Sharma,  from the Lifespan Research Institute, the authors explore growing concerns about the lack of standardization in how frailty is measured in rodent aging studies, which may limit the development of effective interventions targeting age-related decline.

Frailty, a key indicator of deteriorating health in older adults, is increasingly assessed in preclinical models using frailty indexes (FIs). These indexes quantify health deficits, such as reduced mobility, cognitive decline, or physical weakness. However, this perspective highlights that FI methodologies vary significantly across studies, from the selection of parameters to the cut-off thresholds used, resulting in inconsistent outcomes that affects reproducibility and translational value.

The authors reviewed 18 rodent studies and found substantial variation in how frailty is defined and measured. Some FIs rely on clinical observations, such as appearance or beahaviour, while others focus on physical performance metrics like grip strength or locomotion. In several cases, applying different FIs to the same group of animals produced contradictory results, underscoring the importance of harmonized protocols.

To illustrate these issues, the researchers applied an 8-item FI to mice of different ages and found that even young mice were sometimes scored as frail, depending on the scoring method and reference values. This finding emphasizes the need for consistent baselines and controlled environments, especially when comparing across studies. The authors recommend using each animal as its own baseline in longitudinal studies, a strategy that enhances reliability without adding significant cost.

“Sex as a biological variable in FIs is an important consideration, as there is a known difference between male and female frailty onset and progression.” 

The authors also discuss emerging automated tools, such as video-based open-field testing, which can reduce observer bias and improve reproducibility. In the future, broader health indicators, such as cognition, circadian rhythms, social behavior, and body composition, may further enhance frailty assessments.

Overall, this work underscores the urgent need for standardized, transparent, and reproducible methods for evaluating frailty in preclinical aging studies. Improved consistency in frailty scoring will better inform the development of healthspan-extending therapies and enhance the translational relevance of animal models.

DOI - https://doi.org/10.18632/aging.206307

Corresponding authors - Abdelhadi Rebbaa - rebbaa@gmail.com, and Amit Sharma - amit.sharma@sens.org

Abstract video - https://www.youtube.com/watch?v=eha3XA9LyWA

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Keywords - aging, frailty, rodents, frailty index, phenotype

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Standardizing Frailty Indexes to Improve Preclinical Aging Research

BUFFALO, NY — October 7, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 27, 2025, titled, “Deregulated miR-145 and miR-27b in Hutchinson-Gilford progeria syndrome: implications for adipogenesis.”

In this study, led by first author Felix Quirin Fenzl and corresponding author Karima Djabali from the Technical University of Munich (TUM), researchers identified that miR-145-5p and miR-27b-3p interfere with the formation of fat cells in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare and fatal premature aging disorder. Their findings help explain why patients often experience fat loss and related metabolic complications and suggest new potential therapeutic strategies.

Hutchinson-Gilford progeria syndrome is a genetic condition that causes rapid aging in children, often leading to early death due to heart disease. Although affected children appear healthy at birth, they soon develop signs of accelerated aging, including hair loss, stiff joints, and a significant reduction in fat tissue. While certain treatments can slow disease progression, many aspects, such as the loss of fat tissue, remain poorly understood.

“Overall, this study provides the first comprehensive miRNA profiling of HGPS and control fibroblasts across different stages of cellular senescence.”

This study focused on how microRNAs—tiny molecules that help regulate gene expression—contribute to the disease. To explore this, the researchers used skin-derived stem cells from both healthy individuals and HGPS patients. When they transformed these cells into fat cells, the HGPS-derived stem cells formed significantly fewer fat cells. This difference was linked to unusually high levels of miR-145-5p and miR-27b-3p. These molecules were found to silence important genes required for fat cell growth and function. When the researchers blocked these microRNAs, fat cell formation improved. 

The team also examined fat tissue from a mouse model of HGPS. Similar to the human cells, these mice showed increased levels of miR-145-5p and miR-27b-3p and impaired fat development. These results confirm that these two microRNAs play a central role in the loss of fat tissue seen in the disease. Importantly, reducing their activity could become a promising therapeutic strategy for restoring fat tissue in affected individuals.

Although further research is needed before developing treatments, this study represents a step forward in understanding the molecular causes of lipodystrophy, a condition in which the body cannot form healthy fat tissue, in HGPS. It also opens the door for future therapies that could improve quality of life and health outcomes for patients. In the long term, similar approaches might benefit people with other metabolic diseases, such as obesity or diabetes, where fat cell function is also disrupted.

DOI - https://doi.org/10.18632/aging.206309

Corresponding authors - Karima Djabali — djabali@tum.de

Abstract video - https://www.youtube.com/watch?v=b0ksC3cvdZ0

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Keywords - aging, Hutchinson-Gilford progeria syndrome (HGPS), progerin, microRNAs, adipogenesis

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Overactive MicroRNAs Block Fat Cell Development in Progeria

Tom Hirons - 'Sometimes a Wild God'
Read by Liam Strain

https://tomhirons.com/poetry/sometimes-a-wild-god

I have loved this poem. I have lived this poem. Now, I have shared this poem. 
Go give the writer some love. 

All rights to the author - Tom Hirons and Feral Angels Press
https://tomhirons.com/
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CAD E100S/dbx286s/Motu M4

Sometimes a Wild God - Tom Hirons

When I hit 50, my life came crashing down. I experienced a slew of mental health and physical health challenges. I can say, the last few years have been hell.

The Middle Age Challenge: Mental and Physical Health

Dr. Leonard Egede, Dr. Rebekah Walker, and Dr. Obinna Ekwunife from the Department of Medicine at the University of Buffalo, NY, describe their #research paper #published in Volume 17, Issue 8 of Aging-US, entitled “Longitudinal relationship between social and CVD risk factors in older adults with prediabetes: the HRS 2006-2016.”
#interview #authorinterview #aging #prediabetes #cardiovascular #health #openaccess #openscience #peerreviewed #journal #publication #publishing #meded

DOI - https://doi.org/10.18632/aging.206308

Corresponding author - Leonard E. Egede - legede@buffalo.edu

Video interview - https://www.youtube.com/watch?v=1MSTk3GQAGA

Video transcript - https://aging-us.net/2025/10/08/behind-the-study-social-and-cardiovascular-risk-factors-in-older-adults-with-prediabetes/

Abstract

Background: This study examines how multiple social risk factors influence cardiovascular disease (CVD) risk control over time in older adults with prediabetes using a nationally representative cohort.

Methods: Data from the Health and Retirement Study (HRS) included 5,086 U.S. adults aged 50+ with prediabetes. Five social risk domains (economic stability, environment, education, healthcare, and social context) were examined as independent variables, while CVD risk factors included glycemic control (HbA1c), systolic blood pressure (SBP), and cholesterol ratio (total cholesterol/high-density lipoprotein). Mixed-effects models assessed relationships between social risk factors and CVD outcomes, adjusting for age, gender, race, and marital status.

Results: The sample had an average age of 68.6 years, with 60.2% female, and 70.97% identifying as non-Hispanic Black. Average HbA1c was 5.7, SBP 129.4, and cholesterol ratio 3.85. Limited education was consistently associated with increased CVD risk—HbA1c (β = 0.03, 95% CI: 0.01–0.06, p < 0.001), SBP (β = 4.34, 95% CI: 2.96–5.71, p < 0.001), and cholesterol ratio (β = 0.08, 95% CI: 0.01–0.16, p < 0.05) —in the fully adjusted model. Medication cost-related non-adherence was significantly associated with higher HbA1c levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05). Difficulty paying bills and lack of health insurance were both significantly associated with higher cholesterol levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05) and (β = 0.22, 95% CI: 0.15–0.30, p < 0.001), respectively.

Conclusions: Social risk factors, particularly limited education, significantly impact CVD risk in older adults with prediabetes.

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Keywords - aging, prediabetes, social determinants of health, health equity, cardiovascular health, population health

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Behind the Study: Social and Cardiovascular Risk Factors in Older Adults with Prediabetes

BUFFALO, NY — October 9, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 22, 2025, titled, “The impact of long-term social housing on biconditional association task performance and neuron ensembles in the anterior cingulate cortex and the hippocampal CA3 region of aged rats.”

The research team led by Anne M. Dankert from Providence College and University of North Carolina, Chapel Hill, showed that aged rats who lived in socially enriched environments throughout life retained better memory and cognitive flexibility than those housed alone. This study highlights the importance of social interaction in protecting the aging brain.

Cognitive decline, such as memory loss and reduced problem-solving ability, affects many people over the age of 65. While many factors contribute to age-related cognitive decline, this study suggests that one key factor may be surprisingly simple: long-term social connection. To explore how social interaction might influence memory performance and brain activity, the researchers designed a study using rats as a model for aging in humans.

“Cognitive decline and changes in neuronal activity are hallmarks of aging.”

They compared three groups of rats: young adults, aged rats housed alone, and aged rats housed socially in groups. All groups had access to the same physical enrichment, such as exercise and stimulating objects, but only some experienced lifelong social companionship. The team tested these animals on a complex memory challenge known as the biconditional association task, which requires animals to make context-based decisions—an ability that typically declines with age.

The results showed that aged rats living in social groups performed just as well as young adults on the memory task, while those housed alone showed significant impairments. Socially housed rats also made fewer working memory errors and required less effort to complete cognitive tasks, suggesting not only better performance but more efficient brain function. These benefits were not observed in aged rats who received only environmental enrichment without social interaction.

Brain imaging revealed additional differences between the groups. Socially housed aged rats showed increased activity in the hippocampus, particularly in the CA3 region, which plays a key role in forming and separating memories. In contrast, aged rats that lived alone had lower activity in this region, which may explain their poorer performance. Interestingly, socially housed rats also showed reduced overactivity in the anterior cingulate cortex—a brain area involved in attention and decision-making—suggesting a more balanced and efficient neural response.

This research provides new insight into how lifelong social experiences shape brain health during aging. While earlier studies have shown that physical activity and cognitive stimulation help preserve cognitive function, this study identifies social interaction as an independent and powerful protective factor. The findings are consistent with human studies showing that older adults who remain socially active tend to experience slower cognitive decline and stronger brain function.

Overall, these results emphasize that brain aging is not inevitable but may be influenced by our social environments. This research suggests that fostering lifelong social connections could be a critical, low-cost strategy to protect memory and mental flexibility in older adults.

DOI - https://doi.org/10.18632/aging.206310

Corresponding author - Anne M. Dankert - adankert@unc.edu

Abstract video - https://www.youtube.com/watch?v=poNnPz1ti6Q

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Lifelong Companionship Protects Aging Rat Brains from Cognitive Decline

The Virginia Center on Aging's podcast, Aging for All, features guests who are dedicated to advancing health, well-being, and equity for elders of today and tomorrow.

During the day, I’m a radio host working for public media in Rhode Island. I’ve spent almost 30 years of my life as a broadcast journalist, most of it in radio. I’m fascinated by people who want to share their stories, and everybody’s got a story to share. ￼

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

Voiceover artist for storytelling, corporate, and advertising, and a field recording enthusiast.

New tracks tagged #Aging