Fight Aging! Newsletter, July 1st 2024

Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220-250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow.

Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1, and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin.

In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.

Cryopreservation is currently the main method for the long-term storage of cells and tissues. At extremely low temperatures, the diffusion is slow, and molecules do not have enough energy to pass energy barriers for chemical reactions. Therefore, biological activity practically ceases, and the cells and tissues can be preserved. However, ice growth during the cooling and warming stages poses a significant challenge. Intracellular freezing is usually considered to be lethal. Extracellular ice growth leads to water depletion from the solutions, resulting in an elevated solute concentration and diffusion of water out of the cells. This leads to osmotic stress due to heightened intracellular solute concentration, membrane injuries, and physical stress on shrinking cells. Ice recrystallization (IR), the process of enlargement of ice crystals at the expense of smaller crystals, is considered damaging and occurs during the freezing and thawing. The amount of ice and its growth pattern are contingent on the solutes and on the temperature profile through freezing, storage, and thawing.

The primary approach for mitigating ice growth damage in cryopreservation is through vitrification. Vitrification is the conversion of a liquid to an amorphous solid glass without undergoing crystallization. This process occurs through rapid cooling, effectively bypassing the ice growth and nucleation zones between the melting temperature (Tm) and the glass-transition temperature (Tg). The liquid water molecules do not have sufficient time to organize into a crystalline structure and rigidify into a glass state with exceptionally high viscosity. When the target is much larger than a single cell, it is impractical to obtain stable vitrification solely by fast cooling and heating. Vitrification of biological samples involves a combination of rapid cooling and heating rates, in addition to adding cryoprotective agents (CPAs). CPAs depress the melting temperature (Tm) and the homogeneous nucleation temperature (Th) while also elevating the Tg in a concentration-dependent manner. This results in a narrower temperature difference between Tm and Tg, effectively reducing the ice growth and nucleation phases and enabling vitrification at slower cooling rates.

One such approach to mitigate devitrification involves the introduction of various ice-active substances. Ice-binding proteins (IBPs), as suggested by their name, possess an inherent capability to bind to ice crystals and nuclei, aiding organisms in surviving freezing conditions. Through direct interaction with water molecules on the ice surface or at the ice-water interface, IBPs exert significant physical effects on the subsequent growth of the bound ice crystal. IBPs depress the freezing point of an ice crystal in a noncolligative manner by blocking the access of water molecules to the ice surface, resulting in a lower freezing point than the melting point within an IBP solution. This mode of ice growth inhibition markedly differs from the colligative effect of small molecule CPAs used in vitrification. Moreover, IBPs exhibit robust IR inhibition activities.

This study investigates the impact of two distinct IBP types on vitrified DMSO solutions at concentrations relevant to cryopreservation procedures. The IBPs used in our research are antifreeze proteins (AFPs), which are a subset of IBPs that particularly act to depress ice growth and recrystallization. We investigate the impact of two types of antifreeze proteins (AFPs): type III AFP from fish and a hyperactive AFP from an insect, the Tenebrio molitor AFP. We report that these AFPs depress devitrification at -80 °C. Furthermore, in cases where devitrification does occur, AFPs depress ice recrystallization during the warming stage. The data directly demonstrate that AFPs are active at temperatures below the regime of homogeneous nucleation. This research paves the way for exploring AFPs as potential enhancers of cryopreservation techniques, minimizing ice-growth-related damage, and promoting advancements in this vital field.

Adult hippocampal neurogenesis (AHN) has been a prolific topic of research and discussion for the last 30 years. The possibility of neuron renewal and the underlying promise of regeneration in the context of aging and neurological disease has been an important catalyst for the field that have attracted the attention of researchers, funding agencies, scientific journals, and the public. Due to the obvious limitations to perform studies on the human brain, functional inferences about adult neurogenesis have been collected almost exclusively in rodents, mostly in mice.

The functional relevance of new neurons relies on their distinct physiological properties during their maturation before they become indistinguishable from mature granule cells. Most functional studies have used very young animals with robust neurogenesis. However, this trait declines dramatically with age, questioning its functional relevance in aging animals, a caveat that has been mentioned repeatedly, but rarely analyzed quantitatively. In this meta-analysis, we use data from published studies to determine the critical functional window of new neurons and to model their numbers across age in both mice and rats. Our model shows that new neurons with distinct functional profile represent about 3% of the total granule cells in young adult 3-month-old rodents, and their number decline following a power function to reach less than 1% in middle aged animals and less than 0.5% in old mice and rats.

This acute decline of neurogenesis challenges the notion of a prominent functional role even in young adult animals, but particularly in middle aged and old animals, in which neurogenesis reach very low levels, well below 1% and the ratio of activated distinct functional neurons (here meaning new neurons 4-8-week-old exhibiting the differential physiology conferring them enhanced plasticity and excitability) drops to 3-5%. This functional controversy might be in part explained by experimental bias, as most functional studies have been performed in very young, sometimes adolescent rats and mice when they exhibit peak neurogenesis, disregarding the much lower levels of new neurons present in middle aged and old animals. For the same reason, extrapolation of those data to humans might not be very useful, as there might not be much interest in improving cognition of people in their 10s and 20s when they are in their cognitive prime, while it could be relevant to help people say beyond their 60s and 70s, when hippocampal function might take a hit due to aging or neurological disease.

We think our data provides a realistic framework to describe quantitatively adult neurogenesis in murine rodents, and based on these results, we find very difficult to reconcile - from a computational and from a commonsense perspective - that the low number of distinctly functional new neurons might have an essential role in the variety of functions in which they have been involved, a caveat that needs to be addressed in functional models of adult neurogenesis.

Here announcing agingbiotech.info/therapeutics (beta), a table of most available potential anti-aging therapeutics, including supplements, drugs, lifestyle interventions, etc. The goal isn't to judge or rank these therapies but to summarize other evaluations and link useful sources of information.

Important notes: I'm launching it not completely filled out on the assumption it's better to release the substantial info collected so far since many purported therapeutics are commonly discussed and used, but sometimes by people who haven't looked at much info. Many people experiment with the personal use of therapies despite the scientific understanding and evaluation of many being patchy. What data or analysis exists isn't easy to collect. There is no central place to find links to much of the relevant papers and data. This is meant to be one such collection.

The overall philosophy of Aging Biotech Info is that great things are on the way from aging biotech but not yet available. Some people naturally don't want to wait, but one should be cautious of over-interpreting available data for anti-aging therapies. This new table can aid deep dives. It is a jumping off point that is hopefully slightly better than just starting with a web search.

This is absolutely not a recommended "stack", nor a direct endorsement. My sense is that most molecules here don't yet come with enough evidence for most people to use them, especially at super-physiological levels, and the most important column is the who-needs-it column called "best diagnostics/biomarkers to determine individual need and to titrate dose", for which there are woefully inadequate answers for most things. I think that a lot of people overestimate how much good many supplement or drug molecules will do. Simultaneously my sense is that the lifestyle intervenations are woefully underestimated and underutilized, as well as being mostly safer.

I hope that this is useful to some people. Those who want to help fill in the missing details should reach out directly.

As with any complex system, hematopoietic stem cells lose functionality as they age - and, in the process, contribute to the risk of serious diseases, including blood cancers. We know that the risk of developing aging-associated diseases is different among different individuals. Surprisingly, however, little is known about whether hematopoietic stem cells age differently between individuals. This is in part because these hematopoietic stem cells are so rare, researchers typically pool all of these stem cells together, studying them in aggregate.

Researchers recently studied hematopoietic stem cells at the single cell level in nine individual, genetically identical middle-aged mice - offering the first close look at how subtle changes in the bone marrow microenvironment ages hematopoietic stem cells across individual mice. Researchers found that despite the mice being all the same age, the hematopoietic stem cells in the bone marrow of these individual mice aged differently. But that's not all. The team could predict the function of the hematopoietic stem cells based on the activity of two growth factors that are also present in humans.

The two growth factors - Kitl and Igf1 - are produced by mesenchymal stromal cells (MSC) that surround the stem cells in the bone marrow microenvironment. By profiling the RNA transcriptome in these MSCs across individual mice, researchers found that the decline of these growth factors correlated with age-associated molecular programs in hematopoietic stem cells.

Here, we generated individual single cell transcriptomic profiles of hematopoietic and non-hematopoietic cell types in five young adult and nine middle-aged C57BL/6J female mice, providing a web-accessible transcriptomic resource for the field. Among all assessed cell types, hematopoietic stem cells (HSCs) exhibited the greatest phenotypic variation in expansion among individual middle-aged mice. We computationally pooled samples to define modules representing the molecular signatures of middle-aged HSCs and interrogated which extrinsic regulatory cell types and factors would predict variance in these signatures between individual middle-aged mice.

Decline in signaling mediated by ADIPOQ, KITL and IGF1 from mesenchymal stromal cells (MSCs) was predicted to have the greatest transcriptional impact on middle-aged HSCs, as opposed to signaling mediated by endothelial cells or mature hematopoietic cell types. In individual middle-aged mice, lower expression of Kitl and Igf1 in MSCs highly correlated with reduced lymphoid lineage commitment of HSCs and increased signatures of differentiation-inactive HSCs. These signatures were independent of expression of aging-associated pro-inflammatory cytokines. In sum, we find that Kitl and Igf1 expression are co-regulated and variable between individual mice at middle age and expression of these factors is predictive of HSC activation and lymphoid commitment independently of inflammation.

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans.

The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits.

The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.

Transcription factors (TFs) regulate gene expression and impact on a number of aging drivers, thus playing a crucial role in molding the longevity of an animal. Xbp1 is an evolutionary conserved TF that acts in the IRE1 branch of the endoplasmic reticulum unfolded protein response pathway (UPRER) and has a key role in maintaining cellular proteostasis.

Cellular ability to maintain the health of the proteome (proteostasis) declines with age, in part due to blunted activation and compromised capacity of the proteostasis-ensuring pathways, such as UPRER. Indeed, studies in worms have shown that Xbp1s overexpression solely in the intestine or pan-neuronally can increase lifespan. In both cases, Xbp1s stimulates the activation of UPRER in older animals. The lifespan extension is coupled with a metabolic shift and increased lysosomal activity in the intestine, which acts in concert with UPRER activation to maintain proteostasis. Indeed, Xbp1 is also required for the longevity and improved ER stress resistance of a daf2 mutant. Hence, Xbp1 with its canonical UPRER role contributes to longevity in worms.

Our recent work identified a pro-longevity effect of Xbp1 in Drosophila, where we found that Xbp1s overexpression in the gut and fat body can extend lifespan. In the current study we further characterize the role of Xbp1 in fly longevity. Surprisingly, Xbp1s induction triggered distinct gene expression programs in the two organs. Xbp1s's activity in the gut aligned with its canonical role in activating UPRER, and the activation of Xbp1s solely in the intestinal stem cells was sufficient to increase lifespan. In the fat body, Xbp1s regulated genes involved in metabolism and this activity was also sufficient to promote longevity.

Since 1958, Sweden has registered all cancer patients in the National Cancer Register. Swedish researchers have now used this register to study all cancer survivors who had cancer as a child, adolescent, or adult to examine outcomes in later life. The study's data spans 63 years. From this data, approximately 65,000 cancer patients under the age of 25 were compared with a control group of 313,000 individuals (a ratio of 1:5), where age, sex and housing situation were matched with the patient group. From other registers, the researchers retrieved information on morbidity, mortality and demography.

The researchers found that the cancer survivors were about three times more likely to develop cancer later in life, 1.23 times more likely to have cardiovascular disease and had a 1.41 times higher risk of accidents, poisoning, and suicide. At present, the healthcare system usually follows up cancer survivors five years after the end of treatment. In other words, you are usually considered healthy if the cancer has not returned after five years, and no further follow-up is planned. But the current study, and also previous ones, show that this is probably not enough.

Researchers found consistently that in species where offspring survival depends on the longer-term presence of the mother, the species tends to evolve longer lives and a slower life pace, which is characterized by how long an animal lives and how often it reproduces. "As we see these links between maternal survival and offspring fitness grow stronger, we see the evolution of animals having longer lives and reproducing less often - the same pattern we see in humans. And what's nice about this model is that it's general to mammals overall, because we know these links exist in other species outside of primates, like hyenas, whales, and elephants."

The researchers constructed a universal mathematical model that demonstrates the relationship between the maternal survival and fitness of offspring on the one hand, and on the other, pace of life. Two additional empirical models incorporate the types of data about maternal survival and offspring fitness collected by field ecologists. The hope is that these models can be further tested and utilized by field ecologists to predict how maternal care and survival impacts the evolution of a species' lifespan. "We hope we've made the model straightforward enough, that field ecologists can take their existing long-term demographic data that they've been collecting for decades and apply it to this model, and come up with this estimate of how much they expect mother's maternal care to have shaped the evolution of their study system."

The work builds off the Mother and Grandmother hypothesis, based on observations in 18th- and 19th-century human populations, that offspring are more likely to survive if their mothers and grandmothers are in their lives. The new models are both broader and more specific, incorporating more of the ways that a mother's presence or absence in her offspring's life impacts its fitness. The team makes predictions, based on research on baboons and other primates, about how offspring fare if a mother dies after weaning but before the offspring's sexual maturation, which researchers have found leads to short-term and long-term, even intergenerational, negative effects on primate offspring and grand-offspring.

Transposons, genes that can relocate to different parts of the genome, are repressed earlier in life but get more active with age and are associated with age-related disease and decline. A new study highlights how transposons - commonly called "jumping genes" because of their ability to move to different parts of the genome - are associated with age-related disease and decline, as well as how additional genes governing transposon expression may one day be therapeutic targets for aging. Transposons make up approximately 45% percent of human DNA, and their activity is largely repressed in younger, healthy cells. However, with age, these genes are expressed more and become more mobile, correlating with various age-related declines in function

Researchers focused on long interspersed element 1 (LINE-1), a family of transposons that collectively make up about 17% of the human genome. Previous studies have shown that, like other transposons, LINE-1 also appears to be expressed more with age and in aging-related disease. The researchers worked with human cells in vitro to see how overexpression of the suspected regulatory genes affected the activity of LINE-1. Engineering cells to overexpress two of the genes, IL16 and STARD5, markedly increased overall LINE-1 expression. In addition, treating normal cells with a short-term exposure to IL16 protein also induced higher expression of LINE-1. "These are new validated regulators of transposable element activity, and they are potential targets for aging."

Regulating jumping genes is a new job description for both of these genes, but their potential connections to aging make sense. STARD5 is involved in moving cholesterol within cells and is upregulated in response to stress in the endoplasmic reticulum (ER) - an organelle involved in protein synthesis and lipid metabolism. "Aging is often accompanied by changes that can promote ER stress. Given its role, it's possible that STARD5 is involved in age-related alterations," Bravo said. "Interestingly, we observed that upregulating STARD5 led to an upregulation of IL16, suggesting that there may be a synergy between the two in activating transposons."

IL16 is mainly known for its role in regulating immune responses to infection, though they found that its blood levels increase with age. Connections between jumping gene activity and immune responses aren't far-fetched - evolutionary biology research has indicated that transposons are descendants of ancient viruses that took up residence in cells. In addition, chronic low-grade inflammation is one of the signs of biological aging, which could be tied to immune responses to transposon expression.

Glaucoma is a kind of progressive optic neurodegeneration characterized by elevated intraocular pressure (IOP), severe eye pain, and irreversible vision loss that could lead to the progress of permanent blindness. Retinal ganglion cells (RGCs) are the neurons that convey visual information and their loss ultimately causes deficits in neuronal function, which is considered the main pathological hallmark of glaucoma. The loss of RGCs is triggered by multiple mechanisms, such as neurotrophic factor deprivation, axonal transport failure, activation of apoptotic signals, mitochondrial dysfunction, oxidative stress, and loss of synaptic connectivity, etc.

It is now confirmed that cellular injuries induced by aging or ischemia can cause unbalanced oxidative stress in mitochondria by producing uncontrolled levels of ROS, leading to severe cell death. DNA damage is involved in RGCs loss by mediating aging, oxidative stress, post-mitotic neurons, as well as glutamate excitotoxicity, and is considered the major form of neurological disorder. Therefore, strategies that halt and repair DNA damage are recognized to be beneficial for reducing RGCs loss in glaucoma.

It is believed that DNA damage is regulated by several mechanisms, such as protein modification and signaling pathway dysfunction. The cGAS-STING pathway is associated with DNA damage sensing, modulation of inflammatory responses, autoimmunity, and cellular senescence. Previous studies showed that inhibition of the cGAS-STING pathway exhibited potential alleviating effects on ischemia/reperfusion injury-induced retinal ganglion cell death. Moreover, diverse effects of the cGAS-STING signaling have been found in mediating ocular diseases including age-related macular degeneration, keratitis, diabetes mellitus, and uveitis. In the present study, we aimed to explore the potential mechanism underlying RGCs loss in glaucoma and the contribution of cGAS/STING signaling to the loss of RGCs in response to DNA stress.

A mouse model of glaucoma was established by injecting hypertonic saline into the limbal veins. In the hypertonic saline-injected mice, we found visual function was impaired followed by the increased expression of γH2AX, a DNA damage marker, and activation of cGAS-STING signaling. We found that DNA damage inducer cisplatin treatment incurred significant DNA damage, cell apoptosis, and inflammatory response. Mechanistically, cisplatin treatment triggered activation of the cGAS-STING signaling by disrupting mitochondrial function. Suppression of cGAS-STING ameliorated inflammation and protected visual function in glaucoma mice. Thus targeting cGAS-STING signaling represents a potential therapeutic strategy for glaucoma.

Post-stroke cognitive impairment (PSCI) is a clinical syndrome characterized by cognitive deficits that manifest following a stroke and persist for up to 6 months post-event. This condition is grave, severely compromising patient quality of life and longevity, while also imposing substantial economic burdens on societies worldwide. Despite significant advancements in identifying risk factors for PSCI, research into its underlying mechanisms and therapeutic interventions remains inadequate.

Recently, the role of microglia in PSCI has garnered increasing attention. Microglia, the brain's primary immune and pro-inflammatory cells, are critical to the central nervous system's (CNS) immune response. Evidence suggests that microglia-mediated neuronal damage and dysfunction play a pivotal role in the pathogenesis and progression of PSCI, involving neuropathological changes post-stroke and several signaling pathways implicated in cognitive deficits, such as TLR4, p25/CDK5, Nuclear factor kappa-B (NF-κB), and CX3CR1.

Moreover, existing studies underscore neuroinflammation as a pivotal mechanism in PSCI, with microglia playing a crucial role within this context. This review reveals that microglial activation can be triggered through multiple pathways, leading to the polarization of activated microglia into two distinct phenotypes: M1 and M2. These phenotypes exert divergent effects on PSCI, with M2 microglia serving a protective function, whereas M1 microglia contribute to detrimental outcomes. Identifying strategies to guide the polarization of microglia towards the M2 phenotype during PSCI progression represents a critical avenue for therapeutic intervention.

In this nested case-control study, individuals aged 80 years or older were evaluated, including 1,454 centenarians and 3,768 individuals who died before reaching 100 years. Individuals with the highest healthy lifestyle score (constructed from smoking, exercise, and dietary diversity) had a significantly higher likelihood of becoming a centenarian, compared with those with the least healthy lifestyle behaviors. Previous studies have reported that lifestyle factors were associated with life expectancy and/or mortality, but most of them studied the middle-aged or older age groups (aged ≥60 years), and few focused on people aged 80 years or older.

A healthy lifestyle score for 100 (HLS-100, ranging from 0 to 6), including smoking, exercise, and dietary diversity, was constructed, with higher scores indicating potentially better health outcomes. he primary outcome was survivorship to becoming a centenarian by 2018 (the end of follow-up). Information on sociodemographic characteristics, lifestyle factors, and other covariates was collected.

During a median follow-up of 5 years, 373 of 1,486 individuals among the lowest HLS-100 (0-2) group and 276 of 851 individuals among the highest HLS-100 (5-6) group became centenarians. The adjusted odds ratio (AOR) comparing the highest vs the lowest HLS-100 groups was 1.61. An association was noted when we further treated centenarians with relatively healthy status as the outcome, as evaluated by self-reported chronic conditions, physical and cognitive function, and mental wellness (AOR, 1.54). Adhering to a healthy lifestyle appears to be important even at late ages, suggesting that constructing strategic plans to improve lifestyle behaviors among all older adults may play a key role in promoting healthy aging and longevity.

Biological age (BA) is the most important risk factor determining individual risk of morbidity and mortality, with true BA of individuals generally different from chronological age (CA). Attempts to construct biological aging clocks, inferring BA from observable physical features (biomarkers), have a long history. BA clocks have been constructed based on different classes of biological features, including clinical parameters, DNA methylation (DNAm) and many types of omics data. Historically, BA is defined as the age at which the test subject's physiology (as determined by its position in feature space) would be approximately normal for the reference cohort. First-generation DNAm clocks follow this approach. Although such clocks have attained impressive accuracy in determining CA, they are not optimized to predict future morbidity and mortality.

Second-generation BA clocks aim to directly predict future mortality from biological parameters. These clocks define true BA as 'Gompertz age', or the age commensurate with an individual's future risk of dying from all intrinsic causes. Second-generation clocks share some similarities with traditional clinical risk markers, such as the atherosclerosis cardiovascular disease (ASCVD) score, but differ in that they predict all-cause mortality, better reflecting the high degree of interconnectivity between organ system and disease etiology. Successful aging is more than the absence of specific diseases. Unlike existing clinical risk markers, BA clocks can identify individuals likely to remain free from age-dependent dysfunction, morbidity, and mortality for years to come. BA clocks can, therefore, provide normative targets for clinical intervention and individual guidance to promote healthy aging.

Second-generation BA clocks require large-scale cohort data comprising data on biological features combined with long disease and mortality follow-up. For standard clinical chemistry and physiological features, datasets meeting these criteria are available, enabling construction of second-generation 'clinical clocks' (CCs), designed to predict future mortality and morbidity directly from clinical features and biomarkers. In settings where the relevant clinical features and blood markers are readily accessible, CCs have distinct advantages. The features on which CCs are built often have intrinsic well-established biological and pathophysiological meaning, making their findings comparatively easy to interpret and act upon clinically. The development and validation of more powerful CCs, as well as tools facilitating their clinical interpretation and application, should, therefore, be a priority.

As we age, the DNA and proteins that make up our bodies gradually undergo changes that cause our bodies to no longer work as well as before. This in turn makes us more prone to getting age-related diseases, such as cardiovascular disease, cancer, and Alzheimer's disease. One important change is that the proteins in our cells can sometimes become misfolded and clump together to form aggregates, so-called amyloids. Misfolding and aggregation can happen to any protein, but a specific group of proteins known as intrinsically disordered proteins (IDPs) are especially prone to forming amyloids. IDPs make up around 30 percent of the proteins in our cells and they are characterized by having no fixed structure. Instead, they are flexible and dynamic, flopping around like strands of cooked spaghetti.

While the molecular mechanisms are widely debated and an important aspect of basic research, scientists know that aggregates formed from IDPs tend to accumulate in many long-lived cells - such as neurons or muscle cells - as we age. Moreover, they can cause many age-related diseases, particularly neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Thus, having many aggregates in a cell could be an indicator of how unhealthy the cell is or if a person is likely to develop an age-related disease soon. In a recently published article, researchers propose that IDP aggregation could be used as a biological "clock" to measure a person's health and age.

"In practice, we are still far away from a routine diagnostic test, and it is important that we improve our understanding of the fundamental mechanisms leading to IDP aggregation. However, we want to stimulate thinking and research in the direction of studying protein aggregates to measure biological ageing processes. We are optimistic that in the future we will be able to overcome the current challenges of reading a protein aggregation clock through more research on IDP dynamics and making further technological developments."