LongeCityNews Last Updated: 02 July 2025 - 07:12 AM

This month, in between reporting on new methods of affecting aging at its most basic levels, we caught up with AI developers and a longevity fund. Here’s what’s happened in June.

LEAF News

Springtime for the Longevity Industry: If you are in the Northern Hemisphere, then spring is well underway and the weather is warming up. This is the season of renewal and growth. With that in mind, let’s take a look at what the Lifespan and LRI team has been up to.

Interviews

Rejuve.AI: Just Another App or a Longevity Research Network?: On its website, Rejuve.AI, a company co-founded by its dynamic CEO, Jasmine Smith, and a renowned AI researcher, Ben Goertzel, promises a lot of things: to “democratize longevity, globally,” to enable you to “take control of your data, and harness its earning potential,” and to “unite against aging.”

Boyang Wang on Targeting Underfunded Longevity Projects: In this interview, Boyang Wang of Immortal Dragons discusses the kinds of projects he wants to fund, ways in which the industry can be encouraged to develop, relationships between the East and West in longevity research and development, and what got him involved in longevity.

Advocacy and Analysis

Longevity Policy, Advocacy in the Spotlight at Vitalist Bay: While the conference did not turn up huge crowds, it was an important first attempt to kick-start a discussion about how the longevity movement can take over the global agenda.

Research Roundup

Blunting an Inflammatory Pathway Slows Alzheimer’s in Mice: Scientists have demonstrated that knocking out part of the cGAS-STING DNA-sensing pathway slows disease progression in a mouse model of Alzheimer’s, calming down microglia and protecting neurons.

Educated ‘Night Owls’ Might Have More Cognitive Decline Risk: A recent analysis of over 20,000 middle-aged and older adults showed an association between a later chronotype (‘night owls’) and cognitive decline among highly educated people.

New Insights Into How Neural Stem Cells Age: Researchers publishing in Aging Cell have used single-cell transcriptomics to discover new insights into how neural stem cells (NSCs) change with aging.

Younger Cohorts Show Less Dementia at the Same Age: While the overall prevalence of dementia might be rising due to population aging, a study has found that today’s older people seem to be less prone to dementia than in the past.

Researchers Find Age-Modulatory Perturbations at Scale: Scientists have developed a new open source transcriptomic aging clock and published their work as a pre-print. The newly identified rejuvenating drugs and gene perturbations could be applied in regenerative medicine and longevity therapies.

New Study Could Pave the Way for Better Cancer Vaccines: Scientists have found that only about 1% of presented tumor antigens come from oncogenic mutations. The remaining 99%, previously overlooked, may offer better treatment targets.

How Gut Microbiota Impact Endothelial Cell Senescence: In a recent study that included data from humans, mice, and cell culture experiments, researchers demonstrated that gut microbes and their metabolites can profoundly influence the senescence of endothelial cells.

Preventing CRISPR From Causing Senescence: Researchers publishing in Cell Reports Medicine have taken a look at what causes CRISPR/Cas9 gene-editing technology to drive cells senescent and investigated a potential method of preventing it.

A Popular Sweetener Adversely Affects Blood Vessels: A new study has lent more support to previous epidemiological data that ties the popular sugar substitute erythritol to elevated cardiovascular risk.

A New Method of Modifying Stem Cells: Researchers have investigated a never-before-used method of transfecting senescent mesenchymal stem cells (MSCs) and published their results In the Cell journal Molecular Therapy Nucleic Acids.

Financial Behavior Might Help Diagnose Dementia Early: By analyzing a large UK dataset, scientists have identified various financial behaviors that might point to dementia years before it leads to loss of financial capacity.

Longer Reproductive Spans Linked to Younger Brains in Women: Analysis of over a thousand postmenopausal women suggests that women with longer reproductive spans, earlier first period (menarche), and later menopause experience slower brain aging.

Engineering Microglia to Deliver an Anti-Alzheimer’s Drug: In Cell Stem Cell, researchers have described how genetically engineered microglia can be used to deliver therapeutic proteins to the brain.

Senolytics May Treat Some Long-Term Viral Lung Damage: In Aging Cell, researchers have published their findings that mice exposed to influenza experience long-term consequences that can be partially ameliorated with senolytics.

Lipid Metabolite Rejuvenates Muscle Stem Cells in Mice: A recent study investigated the effect of a single treatment of prostaglandin E2 on improving muscle strength and rejuvenating muscle stem cells in mice.

Targeting an Inflammatory Pathway Fights Alzheimer’s: Scientists have discovered that a rare mutation protects against Alzheimer’s disease by dampening a central inflammatory pathway. They recapitulated these results using a small molecule.

How Part of the Krebs Cycle Affects Senescence: Researchers have discovered how and why α-ketoglutaric acid (AKG) affects cellular senescence and how a small molecule may be useful in affecting this process.

Subcutaneous and Visceral Fat React Differently to Obesity: Scientists have found that visceral fat and subcutaneous fat produce different responses to obesity in male mice and human patients and identified an important regulator of these processes.

Researchers Identify a New Dementia Target: Researchers have ascertained that excessive amounts of complement C3, an essential immune protein that increases with aging, are responsible for causing dementia in a mouse model.

The molecular impact of cigarette smoking resembles aging across tissues: This multi-tissue and multi-omic analysis of the effects of cigarette smoking provides an extensive characterization of the impact of tobacco smoke across tissues.

Long-term fasting and its influence on inflammatory biomarkers: A comprehensive scoping review: Results differ based on study design, fasting protocol, participant health status, and inflammatory baseline.

Enhancing active aging through exercise: a comparative study of high-intensity interval training and continuous aerobic training benefits: Future research should focus on longitudinal studies to assess the durability of these benefits and explore combining HIIT and CAT for optimal outcomes.

Coffee Consumption Is Associated With Later Age-at-Onset of Parkinson’s Disease: This relationship appears to be causal, although there is no evidence of an association with Parkinson’s risk or progression.

Green tea consumption and dementia risk in community-dwelling Japanese people aged 40–74 years: Higher consumption of green tea is independently associated with a lower risk of dementia.

Daily low-dose aspirin halves incident type 2 diabetes in elderly subjects with prediabetes: Daily treatment with 100 mg aspirin was associated with approximately a 50% reduction in the incidence of new-onset Type 2 diabetes, but also with an increased risk of gastrointestinal bleeding, in elderly individuals with prediabetes.

Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial: NR may be beneficial for preventing atherosclerosis, skin ulcers, and kidney dysfunction in patients with Werner syndrome.

Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis: Overall, this study suggests that rapamycin and dietary restriction confer comparable lifespan extension across a broad range of vertebrates.

Senotherapy as a multitarget intervention in chronic obesity: In this study, sulforaphane was more broadly effective than the well-known combination of dasatinib and quercetin.

A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice: These results suggest that non-genotoxic hematopoietic stem cell ransplantation could fundamentally change the clinical management of age-associated hematological disorders

Intrinsic health as a foundation for a science of health: These researchers provide a definition of intrinsic health as a quantifiable property of individuals that declines with age and interacts with context.

News Nuggets

Longevity Manhattan Project Launches: San Francisco, June 20: Viva.city and BerlinHouse have opened Viva Frontier Tower, a 6-week popup village in the newly purchased 16-floor Frontier Tower in downtown San Francisco.

Coming Up

6th TimePie Longevity Forum: As China’s population ages rapidly, the development of the longevity industry has been prioritized to the level of national strategy since 2024. To drive its growth, government policies support a broad spectrum of longevity innovations, ranging from preventive wellness to nutritional supplements.

Leakage of DNA fragments from either the nucleus or mitochondria into the cell cytosol is characteristic of a wide range of forms of cell stress, dysfunction, and damage. One component of the innate immune system is that all cells incorporate mechanisms to recognize the presence of inappropriately localized DNA and raise the alert via the secretion of inflammatory signals. This is in part a defense against bacterial and viral infection, but the mechanisms are sufficiently non-specific to also react to a cell's own DNA when it is mislocalized. This is an important mechanism in converting molecular damage and stress into a broader call to the immune system for assistance in a specific location.

The interaction between cGAS and STING is one amongst a number of innate immune pathways that sense molecular damage. cGAS is a sensor for DNA in the cytosol, and its interaction with STING then drives the consequence changes in cell state and inflammatory signaling. Researchers are increasingly interested in the cGAS-STING pathway as a target to suppress maladaptive overactivation of the immune system in aged tissues and inflammatory diseases. Unfortunately, as for all such efforts at present, cGAS-STING interactions are also involved in the normal, beneficial activation of the immune system. This presents challenges and limits the use of a very aggressive suppression of those regulatory systems known to be involved in the chronic inflammation of aging. Better approaches are needed, aimed at removing the damage of aging that causes of STING activation.

Photoaging: UV radiation-induced cGAS-STING signaling promotes the aging process in skin by remodeling the immune network

Excessive exposure of the skin to UV radiation (UVR) accelerates the aging process and leads to a photoaging state which involves similar pathological alterations to those occurring in chronological aging. UVR exposure, containing both UVA and UVB radiation, triggers cellular senescence and a chronic inflammatory state in skin. UVR promotes oxidative stress and a leakage of double-stranded DNA (dsDNA) from nuclei and mitochondria into the cytoplasm of keratinocytes and fibroblasts. It is recognized that cytosolic dsDNA is a specific danger signal which stimulates cytoplasmic DNA sensors. The activation of the signaling through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) is a major defence and survival mechanism combatting against tissue injuries.

There is abundant evidence that UVR exposure of skin stimulates cGAS-STING signaling which promotes cellular senescence and remodels both the local and systemic immune network. cGAS-STING signaling activates the IRF3 and NF-κB signaling pathways which trigger both pro-inflammatory and immunosuppressive responses. Moreover, cGAS-STING signaling stimulates inflammatory responses by activating the NLRP3 inflammasomes. Senescent fibroblasts secrete not only cytokines but also chemokines and colony-stimulating factors which induce myeloid differentiation and recruitment of immune cells into inflamed skin.

Photoaging is associated with an immunosuppressive state in skin which is attributed to an expansion of immunosuppressive cells, such as regulatory T cells. UVR-induced cGAS-STING signaling also stimulates the expression of PD-L1, a ligand for inhibitory immune checkpoint receptor, which evokes an exhaustion of effector immune cells. There is clear evidence that cGAS-STING signaling can also accelerate chronological aging by remodeling the immune network.

Some forms of respiratory infection can cause lasting issues and loss of function. It has been suspected that an increased burden of senescent cells is one of the mechanisms involved in post-infection effects. While senescent cells are created constantly throughout life, a population of lingering senescent cells grows with age to disrupt tissue structure and function via inflammatory signaling. An increase in this burden of senescent cells is already known to cause increased mortality and risk of age-related disease in cancer survivors treated with chemotherapy and radiotherapy, so it should not be surprising to find this outcome occurring in other conditions and treatments that place a great deal of stress on cells for an extended period of time.

Influenza A virus (IAV) infection causes acute and long-term lung damage. Here, we used immunostaining, genetic, and pharmacological approaches to determine whether IAV-induced cellular senescence causes prolonged alterations in lungs. Mice infected with a sublethal dose of H1N1p2009 exhibited cellular senescence, as evidenced by increased pulmonary expression of p16, p21, β-galactosidase and the DNA damage marker gamma-H2A.X. Cellular senescence began 4 days post-infection (dpi) in the bronchial epithelium, then spread to the lung parenchyma by 7 and 28 dpi (long after viral clearance), and then declined by 90 dpi. At 28 dpi, the lungs showed severe remodeling with structural bronchial and alveolar lesions, abrasion of the airway epithelium, and pulmonary emphysema and fibrotic lesions that persisted up to 90 dpi.

In mice and nonhuman primates, persistence of senescent cells in the bronchial wall on 28 dpi was associated with abrasion of the airway epithelium. In p16-ATTAC mice, depletion of p16-expressing cells with AP20187 reduced pulmonary emphysema and fibrosis and led to complete recovery of the airway epithelium at 28 dpi, indicating a marked acceleration of the epithelial repair process. Treatment with the senolytic drug ABT-263 also accelerated epithelial repair without affecting pulmonary fibrosis or emphysema. These positive effects occurred independently of viral clearance and lung inflammation at 7 dpi. Finally, AP20187 treatment of p16-ATTAC mice at 15 dpi led to complete recovery of the airway epithelium at 28 dpi.

Thus, virus-induced senescent cells contribute to the pulmonary sequelae of influenza; targeting senescent cells may represent a new preventive therapeutic option.

Link: https://doi.org/10.1111/acel.70140

Infectious disease is a major cause of late life mortality, the result of the age-related decline of immune function. The sizable investment in time and funding that goes into efforts to enhance the efficacy of vaccines in older adults is one example of the costs of attempting to cope with the consequences of aging. Developing new vaccines and better vaccination techniques is an expensive process. Yet coaxing the aged immune system into greater efforts via the use of adjuvants and other more sophisticated vaccine engineering cannot produce the degree of benefit that a much more crude vaccination will produce in a younger adult - one is inherently limited by the aging of the immune system. This is one of many areas in which rejuvenation of youthful function is a far better goal to aim for.

Older persons (65 and above) comprise the world´s fastest-growing age group today. Enabling older individuals to live independently, remain socially engaged, and manage or prevent chronic illnesses contributes to reducing healthcare costs and improving overall quality of life. Infectious diseases are a major cause of morbidity and mortality in the older population. In 2021, COVID-19 alone was the third most frequent cause of death for people over 65 (10.9% of all deaths) in the EU. This highlights the devastating effect infectious diseases can have on older populations. Co-morbidities, such as chronic heart or lung disease and diabetes, further increase the risk for severe infections.

The overall morbidity of infectious diseases in older adults is frequently underestimated. In addition to the immediate impact of the acute disease, there are several other risks and sequelae associated with infections in this age group. Many older persons do not recover fully after an acute episode of infection. A study in Canada reported 12% mortality in patients aged 65 and older hospitalized for influenza infection, and 20% suffered a decrease in their functional status (9% moderate decrease, 11% catastrophic disability) after recovery.

Therefore, preventing infectious disease is an important measure to ensure healthy aging and preserve the quality of life. Vaccines against influenza and pneumococcal disease have long been available. This review focuses on novel developments regarding vaccines for older adults including strategies to improve and advance existing vaccines and the recent development of vaccines against additional pathogens, such as Respiratory Syncytial virus. There are still many additional pathogens, for which vaccines are highly desirable for older adults. Age-associated changes of the immune system can impair the immunogenicity and protective effect of vaccines and therefore specific strategies to protect this vulnerable population are necessary.

Link: https://doi.org/10.1080/21645515.2025.2517931