⏳Longevity Signals📈
July 15, 2025
Note: This is not medical advice. Please consult your physician before making changes to your health routine.
🩺 Longevity + Treatments 💪
Researchers have developed a platform for identifying longevity interventions, identifying compounds including selumetinib, vorinostat, celastrol, AZD-8055, LY-294002 that extended lifespan and/or healthspan in male mice. This approach accelerates geroprotector discovery, offering a scalable way to target conserved longevity pathways.
Psilocybin, a psychedelic compound found in hallucinogenic mushrooms, extends cellular lifespan and promotes longevity in aged mice, making it a potential geroprotective agent. Psilocin, its active metabolite, delays cellular aging, reduces DNA damage, and decreases oxidative stress.
A study on plasmapheresis, a procedure removing pro-aging factors from blood, found it alters several biomarkers but does not rejuvenate based on epigenetic clock measurements. Instead, it may accelerate epigenetic aging, warranting more research into the long-term safety of this protocol.
Physical activity, exercise, and fitness may delay or reverse epigenetic aging, extending healthspan. Observational studies show inverse relationships between cardiorespiratory fitness and epigenetic age acceleration, while interventional studies suggest structured exercise can induce epigenomic rejuvenation, especially in blood and skeletal muscle.
Maraviroc is identified as a potential senotherapeutic for treating age-associated sarcopenia, according to a study profiling cellular senescence in aging human skeletal muscle. The research uncovers the heterogeneity and dynamics of senescence-associated secretory phenotypes (SASPs), demonstrating their prevalence and function in skeletal muscle aging.
Engineered human embryonic stem cell-derived mesenchymal progenitor cells with enhanced FOXO3 activity (SRCs) significantly slow aging across multiple organs in aged cynomolgus macaques. SRC treatment improved cognitive performance, preserved brain structure, protected bone integrity, and rejuvenated immune function. The treatment also showed robust safety.
A CD38-targeting peptide vaccine has demonstrated potential to mitigate ageing-associated characteristics in mice, according to a study. The vaccine triggers a robust T-cell response, selectively eliminates CD38+ myeloid cells in the spleen, and reduces age-related physical and cognitive function decline. It also enhances glucose tolerance, oxygen consumption, and boosts the NAD+/NADH ratio in liver tissues.
Estrogen replacement therapy has been shown to slow aging of the immune system, brain, liver, and arteries. However, the benefits are often overlooked due to misconceptions from historical studies. Early initiation of hormone replacement therapy (HRT), particularly estrogen alone, has potential benefits for cognitive health, reduces the risk of Alzheimer’s disease and Type 2 diabetes.
🧬 Longevity + Science 🧪
PathwayAge, a biologically informed model, improves age estimation and disease association analysis by capturing coordinated methylation changes at the pathway level, linking ageing and disease mechanisms. It shows potential for biomarker development and precision ageing medicine.
Chronic inflammation causes muscle stem cell (MuSC) aging through an epigenetic process that results in ferroptosis, an iron-dependent cell death. By downregulating the enzyme Kmt5a, inflammation disrupts monomethylation of H4K20 in MuSCs, leading to the silencing of anti-ferroptosis genes and as a result, muscle degeneration. However, long-term inhibition of inflammation preserves MuSC numbers and enhances muscle regeneration.
Machine learning prediction models using wearable biosensors and systemic inflammatory biomarkers can predict systemic inflammation following a controlled exposure to a live attenuated influenza vaccine, potentially improving viral upper respiratory tract infections (VRTIs) detection, including in asymptomatic people.
Plasma proteins from specific organs can estimate biological age and predict disease onset, including Alzheimer’s, and mortality, with lifestyle factors and medications affecting organ age estimates. Having a ‘young’ brain or immune system is associated with longevity.
Chemical-induced partial reprogramming can improve key drivers of aging, including genomic instability and epigenetic alterations, and extend lifespan, as demonstrated in aged human cells and C. elegans. This approach has potential for future translational applications.
Epigenetic mechanisms, including DNA methylation (DNAm), play a key role in governing cell fate decisions during development, aging, and disease. Recent advancements in sequencing technologies and epigenetic tools allow for a more comprehensive exploration of these interactions. This understanding could lead to the discovery of new biomarkers and contribute to the development of treatments for age-related diseases.
DunedinPACNI, a new measure derived from cross-sectional brain MRI data, accurately gauges the rate of aging. Faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy, dementia, physical frailty, poor health, chronic diseases and mortality in older adults. It could help researchers explore aging effects and evaluate anti-aging strategies.
🧑🤝🧑 Longevity + Teams 📰
Researchers have created the malddaba database, which compiles age-specific demographic rates for mammals in the wild. It currently contains data from 250 publications on 170 species, enabling comparative demographic analyses. The database will be regularly updated.
BioVie’s drug Bezisterim shows potential to slow or reverse biological aging and neurodegeneration by modulating inflammation and gene changes. Data from a Phase 3 study demonstrated Bezisterim’s ability to alter biological age via anti-inflammatory epigenetic modifications.
Longevity biotech Sironax enters a strategic deal with Novartis to acquire its platform designed for enhanced therapeutic delivery across the blood-brain barrier (BBB). The platform could improve treatment of age-related neurological disorders by enabling better brain penetration of various therapies.
Dr. David Furman, a leading researcher in the field of inflammaging, has developed an inflammation aging clock. His research emphasizes the role of chronic inflammation in age-related diseases and lifespan limitation, and aims to find ways to mitigate these effects.
💡Featured Article 🌟
The study by Shindyapina et al. presents a novel platform for identifying compounds that could potentially extend lifespan and healthspan in mammals, focusing on mice as a model organism. The researchers integrated gene expression biomarkers of longevity with in silico chemical screening, cell culture analyses, and short-term dietary interventions, culminating in lifespan studies in mice. This comprehensive approach led to the identification of several compounds, including selumetinib, vorinostat, celastrol, AZD-8055, and LY-294002, which showed promising results in extending lifespan and healthspan in aged male mice, with limited effects observed in females.
The study’s methodology involved a multi-step process: initially, over 4,000 compounds were screened in silico using the Connectivity Map (CMAP) database to identify those whose gene expression profiles in human cells aligned with known longevity biomarkers. From this, 111 top candidates were selected for further testing in primary human hepatocytes (PHHs). The researchers then narrowed down to 25 compounds for in vivo testing in mice, focusing on their effects on gene expression in liver and kidney tissues. Ultimately, 10 compounds were tested for their impact on lifespan and healthspan in aged mice.
Key findings include the discovery that certain compounds, such as selumetinib and vorinostat, not only extended lifespan when administered to aged mice but also showed potential when given to young, genetically diverse mice. The study highlights the importance of transcriptomic signatures in predicting the efficacy of longevity interventions and underscores the potential for these compounds to target conserved longevity pathways.
This biomarker-driven research offers a scalable and systematic approach to discovering geroprotectors, potentially accelerating the development of interventions that could delay aging and improve healthspan in humans. For individuals interested in experimenting with longevity treatments, this study provides a scientific basis for focusing on compounds that influence gene expression profiles associated with extended lifespan and healthspan. However, it is crucial to note that while these findings are promising, further research and clinical trials in humans are necessary to validate the safety and efficacy of these compounds for human use.
