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Category: life extension

Nivolumab and Ipilimumab Combination Treatment in Advanced dMMR/MSI-H Noncolorectal Cancers

In a nonrandomized phase 2 trial of adults with advanced dMMR/MSI-H noncolorectal cancers, combined nivolumab/ipilimumab showed an objective response rate of 63% and 6-month progression-free survival rate of 71%.

Main Outcomes and Measures The co-primary end points were objective response rate (ORR) and 6-month progression-free survival (6-PFS) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, with the secondary end points being median overall survival (mOS), progression-free survival (PFS), and treatment-related toxic effects.

Results Overall, 52 participants were included. The median (range) age of participants was 62 (29−84) years; 41 (79%) were female individuals and 11 (21%) were male individuals. Overall, 52 patients representing 17 tumor types were enrolled, with the most common tumor type being endometrial cancer (26 [50%]). Twenty-seven patients (52%) were pretreated for metastatic disease. ORR was 63% (95% CI, 50% to 75%) with the median duration of response not being reached and 79% of responses being ongoing. The median PFS and OS have not been reached and the 6-month PFS was 71% (95% CI, 57%-81%). Overall, 12 patients (23%) experienced a grade 3/4 immune-related adverse event.

Conclusions and Relevance This nonrandomized clinical trial found that combined anti–PD-1/CTLA-4 blockade was associated with a high rate of durable responses in dMMR/MSI-H noncolorectal cancers, comparing favorably to published trials using anti–PD-1/programmed cell death ligand 1 monotherapy. Anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab may represent an alternative treatment option to monotherapy in this patient population.

New Mega-Analysis Reveals Why Memory Declines With Age

A landmark international study that pooled brain scans and memory tests from thousands of adults has shed new light on how structural brain changes are tied to memory decline as people age.

The findings — based on more than 10,000 MRI scans and over 13,000 memory assessments from 3,700 cognitively healthy adults across 13 studies — show that the connection between shrinking brain tissue and declining memory is nonlinear, stronger in older adults, and not solely driven by known Alzheimer’s-associated genes like APOE ε4. This suggests that brain aging is more complex than previously thought, and that memory vulnerability reflects broad structural changes across multiple regions, not just isolated pathology.

Published in Nature Communications, the study, “Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change,” found that structural brain change associated with memory decline is widespread, rather than confined to a single region. While the hippocampus showed the strongest association between volume loss and declining memory performance, many other cortical and subcortical regions also demonstrated significant relationships. This suggests that cognitive decline in aging reflects a distributed macrostructural brain vulnerability, rather than deterioration in a few specific brain regions. The pattern across regions formed a gradient, with the hippocampus at the high end and progressively smaller but still meaningful effects across large portions of the brain.

https://www.nature.com/articles/s41467-025-66354-y

Genetic risk for Alzheimer’s and widespread brain shrinkage linked to greater memory loss — even in otherwise healthy adults.

Small RNAs in inherited blindness identified!

Proteostasis in the lifespan of hematopoietic stem cells.

The hematopoietic system represents an excellent model to study how proteostasis (protein homeostasis) influences different cell types within the same tissue. This review focuses on mechanisms of proteostasis that preserve the lifespan of rare hematopoietic stem cells (HSCs).

Although most proteostasis network components are expressed in all cells, their activation and utilization are cell type-specific. HSCs maintain low translation rates and a preference for autophagy over proteasomal degradation to minimize protein stress.

To protect the integrity of the stem cell pool, HSCs are thought to respond to damage by clearing defective organelles and proteins or by eliminating compromised cells through differentiation or apoptosis.

A stressed proteome accelerates HSC aging, and the immune system derived from aged HSCs is suspected to contribute to the decline of other tissues. This highlights the importance of maintaining healthy HSCs to preserve organismal wellbeing.

Several experimental treatments in mouse models have been shown to boost HSC activity in older organisms by enhancing proteostasis.

This promising research opens up new possibilities for interventions that could improve aging through regenerative medicine. sciencenewshighlights ScienceMission https://sciencemission.com/longevity-from-blood-stem-cells

Continue reading “Small RNAs in inherited blindness identified!” | >

The cellular senescence–metabolism axis: emerging insights into T cell dynamics in the context of biological aging

Cell Communication and Signaling — The exponential growth of immunometabolism-related studies in the last 10 years has made it very clear that metabolism is a key player in the effector functions of immune cells. Such is the case in cells with lymphoid origin, as CD4 + and CD8 + T cells undergo a series of metabolic reprogramming steps during their differentiation process, which is associated with a change in their effector characteristics. Only recently have factors such as biological aging and cellular senescence been examined in relation to memory T-cell generation and the metabolic reprogramming that accompanies their differentiation. In this review, we examine the emerging roles of cellular senescence and biological aging in shaping T-cell metabolism and immune function, and how these changes in the T-cell landscape contribute to disease onset. We then discuss recent studies on T-cell metabolic reprogramming to highlight how understanding the impact of senescence on T-cell metabolism may reveal new therapeutic opportunities.

Scientists Discover Natural Longevity Molecule That Restores Memory in Alzheimer’s Models

A longevity-linked metabolite restored key memory processes in Alzheimer’s models, highlighting aging biology as a promising therapeutic target. Singapore ranks among the countries with the longest life expectancy, yet many people spend nearly ten of their later years living with poor health. Res

Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy‐Induced Senescent Cells

In the course of TIS, cells undergo a profound epigenomic reorganization that underlies the development of a senescence-associated phenotype and formation of an inflammatory microenvironment.

Glucocorticoid injection shows little benefit for knee osteoarthritis, clinical trial finds

Researchers in China have found no statistically significant advantage for infrapatellar fat pad glucocorticoid injection over saline for 12-week knee pain change or effusion synovitis volume change in inflammatory knee osteoarthritis.

Osteoarthritis affects approximately 595 million people worldwide, with knee joints identified as the most commonly affected. Symptomatic knee osteoarthritis is linked to physical disability, reduced quality of life, and increased mortality in older adults, while curative drugs remain lacking amid a rising burden tied to aging and obesity.

Some knee osteoarthritis involves inflammation, and inflammation can involve two nearby tissues—the fat pad under the kneecap and the joint lining—that are structurally interconnected and serve as important sources of inflammation in knee osteoarthritis.

This Common Blood Pressure Drug Boosts Lifespan And Slows Aging in Animals

The hypertension drug rilmenidine has been found to slow aging in worms – an effect that, if it translates to humans, could one day help us live longer and stay healthier in old age.

Rilmenidine appears to mimic the effects of caloric restriction on a cellular level, and reducing available energy while maintaining nutrition has been shown to extend lifespans in several animal models.

Whether this translates to human biology, or is a potential risk to our health, is a topic of ongoing debate. Finding ways to achieve the same benefits without the costs of extreme calorie cutting could lead to new ways to improve health in old age.

Scientists Discover Method To Erase Toxic Tau From Human Neurons

Researchers at the University of New Mexico have uncovered an unexpected role for OTULIN, an enzyme best known for its involvement in immune system regulation. The team found that OTULIN also plays a key role in the production of tau, a protein linked to many neurodegenerative disorders, along with brain inflammation and the biological processes associated with aging.

The findings were reported in the journal Genomic Psychiatry. In the study, scientists showed that disabling OTULIN stopped tau from being produced and cleared existing tau from neurons. This was achieved in two ways: by using a specially designed small molecule or by removing the gene responsible for producing the enzyme. The experiments were carried out in two types of cells, including cells derived from a person who had died from late-onset sporadic Alzheimer’s disease and human neuroblastoma cells that are commonly used in laboratory research.

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