LongeCityNews Last Updated: 05 February 2026 - 07:44 AM

Amyloid is a category, referring to proteins that clump together and precipitate from solution to form solid fibrils or other structures. At least hundreds of different proteins are capable of forming amyloids given suitable alterations to their structure or surrounding conditions, but most of the research attention given to this activity is directed towards toxic, pathological amyloids that form in great excess in the context of neurodegenerative conditions (such as amyloid-β, α-synuclein, and tau), followed by the few amyloids outside the brain that do the same to contribute to severe cardiovascular and other conditions (such as transthyretin or medin).

In today's research materials, researchers provide evidence for a specific type of amyloid formation to be involved in the creation and maintenance of long-term memory. This is very different from the basis for pathological amyloidosis, and involves different proteins, but given the research community focus on that amyloidosis, there has perhaps been a tendency to write off all forms of amyloid as harmful byproducts of cellular metabolism. A brief glance at the history of our understanding of biochemistry suggests that this sort of viewpoint is usually mistaken; if a process exists, evolution will eventually lead to its incorporation into some necessary aspect of cell function.

How Brain May Deliberately Form Amyloids to Turn Experiences Into Memories

The prevailing model of memory hypothesizes that a change in synaptic strength is one of the mechanisms through which information is encoded in neuronal circuits. While changes in synaptic strength require alterations in the synaptic proteome, the mechanisms that initiate and maintain these changes in synaptic proteins remain unclear. Molecular chaperones play a critical role in proteome function, and act as an interface between the environment and the proteome. Chaperones guide proteins to attain the correct folded state. It has long been thought that in the nervous system, chaperones help proteins to either fold correctly or prevent proteins from harmful misfolding and clumping.

A new study found that in Drosophila, one of a family of J-domain protein chaperones, CG10375, which they named "Funes", does something unexpected - it allows proteins to change their shape and form functional amyloids that house long-term memory. "This expands the idea of a protein's capacity to do meaningful things, and suggests there is an unknown universe of chaperone biology that we've long been missing." Thus amyloids are not always harmful unregulated byproducts as previously thought. Amyloids can be carefully controlled - serving as tools the brain uses to store information. Ultimately, the research reveals for the first time a critical step in the process of how long-lasting memories endure.

In fruit flies, a prion-like protein called Orb2 (and its relative protein CPEB in mammals) must undergo self-assembly at the synapses, the gap between two neurons, to maintain a memory. Orb2 belongs to a class of nonpathological amyloids, where amyloid formation enables a protein to acquire a new function. Over time, the researchers began to hypothesize that the difference between a harmful and a helpful amyloid may depend on whether Orb2's assembly process is tightly regulated by other proteins.

The researchers discovered Funes by manipulating the concentrations of 30 different chaperones in the fly's memory centers. Flies with increased levels of Funes showed a remarkable ability to remember an odor-reward link after 24 hours - a standard proxy for long-term memory. But the most surprising discovery came at the molecular level. Researchers engineered Funes variants that could bind Orb2 but could not trigger its transition into amyloid and found the flies' long-term memory failed. This indicated that Funes is an essential component for long-term memory formation.

A recent study analyzed data from over 15,000 participants and their intake of 11 vitamins, and the results suggested that higher vitamin intake, particularly of Vitamins C and B2, is associated with slower biological aging [1].

Beneficial molecules

One of the easiest and most accessible ways to improve health and lifespan is to consume a diet and supplements that provide adequate nutrition. Studies conducted in cell cultures and animals suggest that various vitamins, through their antioxidant and anti-inflammatory properties, have beneficial effects against aging processes [2, 3]. Human data suggest that vitamins have specific benefits, including improved lipid levels, better cognition and memory, reduced incidence of age-related macular degeneration, and lower mortality in cancer patients [4, 5, 6].

More granular approach

We recently covered a review that discussed the impact of multivitamins and minerals on health and longevity. That study analyzed the findings from 19 meta-analyses published in the last 25 years. While that study took a broad look at the impact of vitamins and minerals on different aspects of health, this study took a more granular approach and investigated the impact of 11 vitamins (A, B1, B2, B3, B6, B9, B12, C, D, E, and K), from both dietary and supplementary sources, on different aspects of biological aging. The authors used data from 15,050 participants, with a median age of 51 years, who were part of the nationally representative National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018.

The authors used three methods to measure different aspects of biological aging: the Klemera-Doubal method biological age (KDM-BA), PhenoAge, and homeostatic dysregulation (HD), each using multiple different biomarkers to assess the speed of biological aging.

The choice of these aggregated measures of biological aging stems from limitations in previous studies, which often focus on single aging-related outcomes, whereas aging is a process that affects multiple systems. Therefore, measuring the speed of aging using aggregate measures of aging that incorporate multiple biomarkers is an attempt to reflect the complexity of the process.

All together and one-by-one

The epidemiological data on the relationship between vitamin intake and biological aging have limitations; for example, studies often focus on the impact of a single vitamin rather than a vitamin complex, which more accurately reflects reality. Those who investigate vitamins in combination often do not examine the effects of individual ingredients within the mixture. To address this gap, those researchers analyzed both scenarios.

An initial analysis, which divided participants into four quartiles by total vitamin intake, showed that those in the highest quartile were, on average, older, had higher socioeconomic status, and had healthier lifestyles. All three metrics of biological aging showed less accelerated aging in the highest quartile group than in those in the lowest quartile. After adjusting for multiple factors, the highest quartile still showed lower biological age acceleration, as measured by KDM-BA and PhenoAge; however, while there was a trend toward reduced age acceleration, the association was not statistically significant for HD.

The researchers also examined the effects of individual vitamins. Reduced biological aging was observed among individuals in the highest quartile for all vitamins, as measured by PhenoAge, but only for B2, B9, and C Vitamin intake, when measured by KDM. In contrast, analysis of HD didn’t show a significant impact of any vitamin.

Biological aging indicators agreed that among all vitamins tested, Vitamin C was the “primary protective driver.” B2, important for supporting metabolic and immune health, came in second. The researchers suggest that the potent role of Vitamin C might stem from its antioxidant effects, which protect against aging-related oxidative damage.

On the other hand, the results suggest that Vitamins B12 and D may have adverse effects. Vitamin B12 is important for blood and nerve cells health and helps make DNA. Vitamin D has many bodily functions, including calcium absorption in the gut; metabolism of calcium, phosphorus, and glucose; bone growth support, remodeling, and mineralization; reduction of inflammation; modulation of cell growth; and neuromuscular and immune function. The researchers suggest the adverse effects of Vitamin D may be due to the absence of a linear, dose-dependent relationship between Vitamin D intake and biological aging, in which higher doses accelerate aging, but this remains to be tested.

We have previously reported on the complex relationship between Vitamin D and the biology of aging. For example, while studies have linked Vitamin D supplementation to slower epigenetic aging, other research suggests that in some cases Vitamin D supplementation may not be beneficial, as a study published in Aging Cell suggests that administering Vitamin D to Alzheimer’s patients may actually make the problem worse.

Subgroup differences

The effects of vitamin intake were found to vary based on demographic and health characteristics. Males, people with a BMI under 30, current alcohol drinkers, people with lower education levels, people who ate less than 1500 calories a day, and people with comorbidities saw more beneficial effects. These results suggest that “individuals with higher underlying physiological stress or inflammation might derive greater benefit from adequate vitamin intake.”

When an analysis was conducted using only dietary data, the researchers obtained similar results: a protective effect of total dietary vitamin intake and a prominent role of Vitamin C in joint protective effects, highlighting the importance of obtaining vitamins through a healthy, whole-food diet.

Achieving nutritionally adequate levels

This study contributes to the growing body of evidence linking vitamin-rich diets to reduced biological aging. [7,8]. However, supplementation doesn’t have to imply taking excessive amounts, as the authors highlight that the “higher intake in our study primarily corresponds to achieving nutritionally adequate levels: over 90% of participants in the highest intake quartile met the Recommended Dietary Allowance for most vitamins.”

Literature

[1] Zhang, X., Xu, Y., Wang, X., Chen, M., Xiong, J., & Cheng, G. (2026). Association between vitamin intake and biological aging: evidence from NHANES 2007-2018. The journal of nutrition, health & aging, 30(2), 100776. Advance online publication.

[2] Monacelli, F., Acquarone, E., Giannotti, C., Borghi, R., & Nencioni, A. (2017). Vitamin C, Aging and Alzheimer’s Disease. Nutrients, 9(7), 670.

[3] Kaźmierczak-Barańska, J., & Karwowski, B. T. (2024). The Protective Role of Vitamin K in Aging and Age-Related Diseases. Nutrients, 16(24), 4341.

[4] Seddon J. M. (2007). Multivitamin-multimineral supplements and eye disease: age-related macular degeneration and cataract. The American journal of clinical nutrition, 85(1), 304S–307S.

[5] Yeung, L. K., Alschuler, D. M., Wall, M., Luttmann-Gibson, H., Copeland, T., Hale, C., Sloan, R. P., Sesso, H. D., Manson, J. E., & Brickman, A. M. (2023). Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial. The American journal of clinical nutrition, 118(1), 273–282.

[6] Harris, E., Macpherson, H., & Pipingas, A. (2015). Improved blood biomarkers but no cognitive effects from 16 weeks of multivitamin supplementation in healthy older adults. Nutrients, 7(5), 3796–3812.

[7] Canudas, S., Becerra-Tomás, N., Hernández-Alonso, P., Galié, S., Leung, C., Crous-Bou, M., De Vivo, I., Gao, Y., Gu, Y., Meinilä, J., Milte, C., García-Calzón, S., Marti, A., Boccardi, V., Ventura-Marra, M., & Salas-Salvadó, J. (2020). Mediterranean Diet and Telomere Length: A Systematic Review and Meta-Analysis. Advances in nutrition (Bethesda, Md.), 11(6), 1544–1554.

[8] Hu F. B. (2024). Diet strategies for promoting healthy aging and longevity: An epidemiological perspective. Journal of internal medicine, 295(4), 508–531.

Diseases of the eye are often the indication of choice for new, advanced forms of medicine, particularly gene therapies. Delivery to the eye is straightforward and proven, effective doses can be very low, and the structures of the interior of the eye are relatively isolated from the rest of the body. All told, the risk to patients is much lower than would be the case for targeting, say, the liver, which makes it a great deal easier to convince investors and regulators to support such a program. Thus we shouldn't be all that surprised to see that the first clinical trial of partial reprogramming to rejuvenate epigenetic control over nuclear DNA structure and gene expression will focus on regeneration of the damaged retina.

The FDA has given the go-ahead for the first ever human trial of a partial epigenetic reprogramming therapy. The FDA's decision clears an investigational new drug application for Life Bioscience's ER-100, a gene therapy designed to rejuvenate damaged retinal cells in people with serious, age-related eye diseases. The biotech is now preparing to commence a Phase 1 first-in-human study to show its therapy can be delivered safely in patients with open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION).

As a first-in-human trial, Life Bioscience's study is primarily focused on safety and tolerability. Instead of using all four Yamanaka factors, ER-100 employs three of the factors (Oct4, Sox2, and Klf4) delivered transiently to reset age-associated epigenetic markers while keeping cells committed to their original function. By excluding c-Myc, a factor associated with uncontrolled growth, the strategy is intended to lower the risk of tumors that has historically concerned regulators and clinicians. From a safety perspective, the company's preclinical studies in non-human primates demonstrated that ER-100 was well tolerated in NHPs, with no systemic toxicities.

"The therapy uses a doxycycline-inducible system, giving us precise control over when the genes are active and allowing treatment to be paused or stopped if needed. In addition, ER-100 is delivered locally to the eye, limiting systemic exposure. Multiple preclinical animal models have demonstrated controlled gene expression, favorable biodistribution, restoration of epigenetic markers, and improvements in visual function which has collectively provided the foundation for FDA clearance."

Link: https://longevity.technology/news/fda-clears-first-human-trial-of-epigenetic-reprogramming-therapy/

Ferroptosis is a form of programmed cell death associated with iron metabolism. A body of evidence supports a role for excessive ferroptosis in the progression of Alzheimer's disease and other age-related conditions, a maladaptive reaction to forms of age-related damage present in the brain, such as mitochondrial dysfunction, an increased burden of senescent cells, chronic inflammatory signaling, and so forth. Researchers are starting to consider suppression of ferropotosis as an approach to treating neurodegenerative conditions, which leads to papers such as this one, a discussion of the mechanisms by which exercise acts to reduce ferroptosis. That is a step along the road to identifying potential targets for drug development. Attempting to mimic specific outcomes of exercise, calorie restriction, or other environmental effects on metabolism is a widely employed strategy, though it seems unlikely to be capable of more than modestly slowing disease progression or modestly reducing severity.

Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a critical link between cellular senescence and Alzheimer's disease (AD). Senescent cells disrupt iron metabolism, promote peroxidation-prone lipid remodeling, and suppress antioxidant defenses, creating a pro-ferroptotic environment that accelerates neuronal degeneration. This review integrates recent mechanistic evidence demonstrating that these senescence-induced changes heighten ferroptotic susceptibility and drive AD pathology through pathways involving protein aggregation, autophagic failure, and inflammatory synaptic loss.

Importantly, physical exercise has emerged as a pleiotropic intervention that counteracts these ferroptotic mechanisms at multiple levels. Exercise restores iron homeostasis, reprograms lipid metabolism to reduce peroxidation risk, reactivates antioxidant systems such as GPX4, enhances mitochondrial and autophagic function, and suppresses chronic neuroinflammation. Moreover, systemic adaptations through muscle, liver, and gut axes coordinate peripheral support for brain health. By targeting ferroptosis driven by cellular senescence, exercise not only halts downstream neurodegenerative cascades but also interrupts key upstream drivers of AD progression.

These findings position ferroptosis as a therapeutic checkpoint linking aging biology to neurodegeneration and establish exercise as a mechanistically grounded strategy for AD prevention and intervention.

Link: https://doi.org/10.3389/fcell.2025.1742209