Ethereum creator Vitalik Buterin sold large amounts of three meme tokens on Wednesday that he was given for free. Buterin then used proceeds of the sales to support a range of charities, according to public blockchain data. Buterin was given the tokens through a rather unusual token distribution strategy. The developers behind at least three dog-themed tokens - based around the Shiba Inu breed of dog - decided to send half of their tokens to his publicly known Ethereum address. These tokens included Shiba Inu (SHIB), Akita Inu (AKITA) and Dogelon Mars (ELON).

The theory behind this was that the approach was akin to burning the tokens. Presumably, the idea was that Buterin - who owns 333,500 ETH worth around 1.3 billion - wouldn't need the cash and would just sit on the tokens. Buterin appears to have had other ideas, however. Starting a few hours ago, Buterin began sending the tokens in batches to Uniswap and selling them for ETH, creating a total of 15,719 ETH, an amount worth about 63 million.

Following the sales, Buterin sent large amounts of ETH to various charities that support different causes. He gave out more than 16,000 ETH along with some of the dog-themed tokens. The largest tranche - 13,292 ETH - was sent to Givewell, a non-profit charity assessment organization. The Ethereum creator also sent 1,000 ETH and 430 billion ELON tokens (the latter worth 215,000) to the Methuselah Foundation, which focuses on making people live longer. He sent 1,050 ETH to the Machine Intelligence Research Institute, which focuses on ensuring AI has a positive impact.

Disease is considered the most fundamental unit of analysis in medicine. The definition of disease is the object of ongoing philosophical debate between naturalistic, constructivist, and instrumentalist accounts. While there is no consensus on the concept of disease, the notion of disease is central to medicine. Until recently, the function of disease as the focus of medicine has gone unchallenged, due to its intuitive appeal as an obviously plausible target of medical intervention. However, the complexity of most age-related ailments, the fact that elders are affected by concomitant conditions (multimorbidity), and the fact that a great number of age-related symptomatic states escape clear nosological determination, have led some to question the utility of disease as the central focus of medical care.

In a provoking 2004 paper on the "end of the disease era," the authors explicitly criticized disease-centric medicine. They instead propose a more individualized approach that revolves around the clinical trade-offs necessary to manage a complexity of concomitant affections. Instead of treating each disease individually, medicine should strive to treat an individual patient's unique combination of diseases, and the way they affect physical and psychological functioning, as well as daily activities, goals, and life plans. The focus is less on discrete pathologies and survival, than on the reality of how an individual organism becomes diseased and weakened over time.

This post-disease paradigm is an example of a very general explanatory framework: one that considers multimorbidity, as opposed to discrete pathological states, to be the central focus of geriatric medicine. In this account, the health of the ageing person is best understood as the result of multiple concomitant pathologies.

In contrast, understanding health as the absence of disease is not compatible with the idea of measuring and protecting functional trajectories as the focus of geriatric care. From an epistemological point of view, this vision clearly resonates with the explanatory framework of ageing as a plastic phenotype. For researchers working on intrinsic capacity, the disease construct is inadequate for capturing how an individual fares in her environment in functional terms. Function, not disease, is the object of care in this clinical perspective on ageing.

The same applies to the molecular version of the explanatory framework. Researchers in this domain are not interested in linking alterations in metabolic pathways to the manifestation of a given discrete pathology. Their focus is rather on the role of those pathways in maintaining organ functionality over time. This, in turn, can translate into the delayed onset and slowing down of multiple diseases of old age. The longitudinal focus of intrinsic capacity emphasizes prevention over reaction even in the absence of a specific clinical phenotype.

The medicine rapamycin has been shown to extend the healthspan of all organisms it has been tested on - mice, warms, yeast - for decades, and yet to date there has been no trial to sufficiently demonstrate safety and proper dosing for this purpose in humans. It is now time for this to change. With your help, we will be conducting a large clinical trial named Participatory Evaluation (of) Aging (with) Rapamycin (for) Longevity Study, or PEARL, to find out. This will be the first study to see if Rapamycin works as well in humans as it does in mice (for longevity).

Rapamycin works through the mTOR signaling pathway, one of the master regulators of cell metabolism and a key controller of autophagy (recycling in cells). Basically, it tells our cells to switch from growth to repair, and to clean out all the garbage. Not only that, but the quality of the proteins our cells produce increases, which means that there is less garbage in the first place. What all this amounts to is improved health and lengthened life for worms, flies and mice - now it's our turn!

The PEARL trial will follow up to 200 participants over 12 months testing four different rapamycin dosing regimens. It will be double-blind, randomized, placebo-controlled and registered with clinicaltrials.gov. The principal investigator is Dr. James P Watson at UCLA, who was also a PI for the famous TRIIM trial. To ensure safety the participants' blood will be regularly monitored and side effects noted.

A battery of tests and measurements will be taken, both after 6 and 12 months. These will include autonomic health tests, blood tests, body composition tests, fecal microbiome testing, immune and inflammation health tests, methylation age clock testing and skeletal muscle tests. With your help we will find out if and how well rapamycin works to combat human aging. And, armed with a positive result, we will finally be able to help slow down onset of age related damage for you and those who you love and care about.

Aging leads to a progressive functional decline of the immune system, rendering the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this decline remains unclear, however, since markers that label immune cells with classical features of cellular senescence accurately and comprehensively have not been identified.

Using a second-generation fluorogenic substrate for β-galactosidase and multi-parameter flow cytometry, we demonstrate here that peripheral blood mononuclear cells (PBMCs) isolated from healthy humans increasingly display cells with high senescence-associated β-galactosidase (SA-βGal) activity with advancing donor age. The greatest age-associated increases were observed in CD8+ T-cell populations, in which the fraction of cells with high SA-βGal activity reached average levels of 64% in donors in their 60s. CD8+ T cells with high SA-βGal activity, but not those with low SA-βGal activity, were found to exhibit features of telomere dysfunction-induced senescence and p16-mediated senescence, were impaired in their ability to proliferate, developed in various T-cell differentiation states, and had a gene expression signature consistent with the senescence state previously observed in human fibroblasts.

Based on these results, we propose that senescent CD8+ T cells with classical features of cellular senescence accumulate to levels that are significantly higher than previously reported and additionally provide a simple yet robust method for the isolation and characterization of senescent CD8+ T cells with predictive potential for biological age.

Human dermal fibroblasts (HDFs) are the primary cell type in the dermis and are responsible for extracellular matrix (ECM) deposition and remodeling, supplying skin with structural integrity and elasticity. In the process of skin aging, the quantity and proliferation rates of HDFs are declined, and collagen is reduced. On the other hand, matrix-degrading metalloproteinases (MMPs) are increased, degrading and changing the structure of the ECM, which accelerates the breakdown of connective tissue. All of these changes result in the thinning of the dermis, enhancement of wrinkles, and loss of elasticity.

Skin aging is caused by intrinsic factors (e.g., time, genetic factors, and hormones) and extrinsic factors (e.g., ultraviolet (UV) exposure and pollution). Eighty percent of skin aging primarily results from exposure to UV light, which is known as photoaging. Ultraviolet B (UVB) radiation penetrates the epithelial layer and causes DNA damage in the dermis of the skin. However, most UVB radiation directly affects cells in the upper dermis. Compared with HDFs in the lower dermis, more HDFs in the upper dermis suffer UVB-induced DNA damage. Failure of aged-cellular repair results in cell death. Healthy cells are gradually generated to replace the damaged cells to keep homeostasis.

Currently, some clinical studies have shown that autologous fat grafting, nanofat, and adipose stromal cells reduce wrinkles, increase dermal thickness, improve skin elasticity, and whiten skin. Adipose-derived stem cells (ASCs) play an important role in these therapies. ASCs have the ability to differentiate into different cell lineages, such as adipocytes, endothelial cells (ECs), osteocytes, cardiomyocytes, and neurons. In addition, ASCs secrete various biologically active molecules to repair damaged neighboring cells and influence the surrounding microenvironment. ASCs are considered a promising tool for cell-based therapy, especially in skin rejuvenation, wound healing, and scar remodeling. Because ASCs are usually injected into the subcutaneous fat layer, the paracrine effect of ASCs is the main mechanism by which skin rejuvenation occurs. However, the role of the paracrine effect of ASCs on the repair of different UVB-induced damaged HDFs is still unknown.

We hypothesized that ASCs could repair different UVB-damaged HDFs to various degrees via paracrine factors. To induce photoaging and natural aging in vitro and in vivo, HDFs and nude mice were irradiated with UVB light, and the control group received no irradiation. We found that ASCs enhanced HDF cell function. However, nonirradiated HDFs were more robust than UVB-irradiated HDFs after coculture with ASCs. This finding suggests that ASC treatment may more strongly impact HDFs in the lower dermis.

Perhaps the most remarkable animal Methuselahs are among bats. One individual of the species Myotis brandtii, a small bat about a third of the size of a mouse, was recaptured, still hale and hearty, 41 years after it was initially banded. "It's equivalent to about 240 to 280 human years, with little to no sign of aging. So bats are extraordinary. The question is, why?" There are two ways to think about this question. First: What are the evolutionary reasons that some species have become long-lived while others have not? And second: What are the genetic and metabolic tricks that allow them to do that?

The outline of an answer is beginning to emerge as researchers compare species that differ in longevity. Long-lived species, they've found, accumulate molecular damage more slowly than shorter-lived ones do. Naked mole rats, for example, have an unusually accurate ribosome, the cellular structure responsible for assembling proteins. It makes only a tenth as many errors as normal ribosomes. And it's not just mole rats: In a follow-up study comparing 17 rodent species of varying longevity, researchers found that the longer-lived species, in general, tended to have more accurate ribosomes.

One of the principles beginning to emerge from comparative studies of aging is that different species may follow different paths to longevity. All long-lived mammals need to delay the onset of cancer, for example. Elephants do this by having multiple copies of key tumor-suppressing genes, so that every cell has backups if one gene breaks during the wear and tear of life. Naked mole rats, on the other hand, gain cancer resistance from an unusual molecule involved in sticking cells together, while bowhead whales have amped up their DNA-repair pathways.

In a healthy state, these immune cells - known as invariant Natural Killer T (iNKT) cells - function as a surveillance system, eliminating cells the body senses as foreign, including senescent cells, which have irreparable DNA damage. But the iNKT cells become less active with age and other factors like obesity that contribute to chronic disease. The iNKT cells have two attributes that make them an especially appealing drug target. First, they all have the same receptor, which does not appear on any other cell in the body, so they can be primed without also activating other types of immune cells. Second, they operate within a natural negative feedback loop that returns them to a dormant state after a period of activity.

Researchers found they could remove senescent cells by using lipid antigens to activate iNKT cells. When they treated mice with diet-induced obesity, their blood glucose levels improved, while mice with lung fibrosis had fewer damaged cells, and they also lived longer. The results presented for iNKT cells in a mouse model of lung fibrosis offer hope for a potentially fatal disease that often leads to lung transplants. "I think this is a potential immune therapy for senescence and fibrosis. It's a fairly well tolerated therapy, and we just have to get around dosing and trials."

Vegetarians appear to have a healthier biomarker profile than meat-eaters, and this applies to adults of any age and weight, and is also unaffected by smoking and alcohol consumption, according to a new study. To understand whether dietary choice can make a difference to the levels of disease markers in blood and urine, researchers performed a cross-sectional study analysing data from 177,723 healthy participants (aged 37-73 years) in the UK Biobank study, who reported no major changes in diet over the last five years.

Participants were categorised as either vegetarian (do not eat red meat, poultry or fish; 4,111 participants) or meat-eaters (166,516 participants) according to their self-reported diet. The researchers examined the association with 19 blood and urine biomarkers related to diabetes, cardiovascular diseases, cancer, liver, bone and joint health, and kidney function.

Even after accounting for potentially influential factors including age, sex, education, ethnicity, obesity, smoking, and alcohol intake, the analysis found that compared to meat-eaters, vegetarians had significantly lower levels of 13 biomarkers, including: total cholesterol; low-density lipoprotein (LDL) cholesterol - the so-called 'bad cholesterol; apolipoprotein A (linked to cardiovascular disease), apolipoprotein B (linked to cardiovascular disease); gamma-glutamyl transferase (GGT) and alanine aminotransferase (AST) - liver function markers indicating inflammation or damage to cells; insulin-like growth factor (IGF-1), a hormone that encourages the growth and proliferation of cancer cells; urate; total protein; and creatinine (marker of worsening kidney function).

However, vegetarians also had lower levels of beneficial biomarkers including high-density lipoprotein 'good' (HDL) cholesterol, and vitamin D and calcium (linked to bone and joint health). In addition, they had significantly higher level of fats (triglycerides) in the blood and cystatin-C (suggesting a poorer kidney condition).

Microglia are immune cells of the brain, representing the neural tissue's defense system. A large body of evidence shows that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of Parkinson's disease (PD) patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, α-synuclein accumulation, and pro-inflammatory cytokine release.

In the central nervous system (CNS), microglia constitute up to 12% of all cells, and their density changes depending on the brain region. Early studies in mice showed that bone-marrow-derived hematopoietic cells move to the CNS, where they differentiate into microglia-like cells. With innovative conditional cell depletion techniques, it was recently shown that microglia have the ability to self-renew, and that interleukin-1 (IL-1) signaling is enabling this process.

Just like the abundance of microglia is region-specific, microglial morphology varies from brain area to brain area. In a resting state, microglia survey the brain microenvironment and show ramified morphology. Surveillance encompasses multiple functions: clearance of accumulated or deteriorated neuronal and tissue elements, dynamic interaction with neurons whilst regulating the synaptic pruning process, and maintaining overall brain homeostasis. Once activated upon brain damage and certain host or non-host stimuli, microglia are quickly undergoing a morphology change into an ameboid-like form, coupled with the release of inflammatory molecules, cytokines and chemokines. With regard to their activation, microglia are commonly divided into two classes: M1 (pro-inflammatory) or M2 (anti-inflammatory). Even though, by now, it is known that the states of activation are much more heterogeneous and diverse.

New approaches are being developed to determine sub-populations of microglia, mostly through single-cell gene expression studies and by determining fine morphological differences using computational methods. With age, microglia tend to express more IL-1β and they become more phagocytic in nature compared to microglia from younger brains. These phenotypic changes over time can influence their ability to function normally and attain the neuronal homeostasis and support. Eventually, an accumulation of non-functional, senescent microglia could contribute to irreversible and progressive neurodegeneration in PD.

It has been frequently reported that myostatin inhibition increases muscle mass, but decreases muscle quality (i.e., strength/muscle mass). Resistance exercise training (RT) and essential amino acids (EAAs) are potent anabolic stimuli that synergistically increase muscle mass through changes in muscle protein turnover. In addition, EAAs are known to stimulate mitochondrial biogenesis.

We have investigated if RT amplifies the anabolic potential of myostatin inhibition while EAAs enhance muscle quality through stimulations of mitochondrial biogenesis and/or muscle protein turnover. Mice were assigned into ACV (myostatin inhibitor), ACV+EAA, ACV+RT, ACV+EAA+RT, or control over 4 weeks. RT, but not EAA, increased muscle mass above ACV. Despite differences in muscle mass gain, myofibrillar protein synthesis was stimulated similarly in all versus control, suggesting a role for changes in protein breakdown in muscle mass gains.

There were increases in MyoD expression but decreases in Atrogin-1/MAFbx expression in ACV+EAA, ACV+RT, and ACV+EAA+RT versus control. EAA increased muscle quality (e.g., grip strength and maximal carrying load) without corresponding changes in markers of mitochondrial biogenesis and neuromuscular junction stability.

In conclusion, we showed that addition of resistance exercise training, but not dietary EAAs, to the myostatin inhibition further increased muscle mass through the attenuation of muscle protein breakdown with proportionate improvements in muscle strength. Interestingly, addition of dietary EAAs to the myostatin inhibition with or without resistance exercise training improved muscle quality. Thus, dissection of the underlying mechanisms behind the combined positive effect of dietary EAAs and resistance exercise training on muscle mass and quality can shed light on the discovery of effective therapeutics against muscle wasting such as sarcopenia.

Telomerase is an enzyme that in its canonical function extends and maintains telomeres, the ends of chromosomes. This reverse transcriptase function is mainly important for dividing cells that shorten their telomeres continuously. However, there are a number of telomere-independent functions known for the telomerase protein TERT (Telomerase Reverse Transcriptase). This includes the shuttling of the TERT protein from the nucleus to mitochondria where it decreases oxidative stress, apoptosis sensitivity, and DNA damage.

Recently, evidence has accumulated on a protective role of TERT in brain and postmitotic neurons. This function might be able to ameliorate the effects of toxic proteins such as amyloid-β, pathological tau and α-synuclein involved in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the protective mechanisms of TERT are not clear yet. Recently, an activation of autophagy as an important protein degradation process for toxic neuronal proteins by TERT has been described.

This review summarises the current knowledge about the non-canonical role of the telomerase protein TERT in brain and shows its potential benefit for the amelioration of brain ageing and neurodegenerative diseases such as AD and PD. This might form the basis for the development of novel strategies and therapies against those diseases.

As the main cause of disease and death in the modern world, senescence (i.e. aging; not to be confused with replicative or cellular senescence) is one of the major biological and medical challenges of the 21st century. It would therefore be invaluable to understand the central biological mechanisms of senescence and how they give rise to late-life disease, including cardiovascular disease, many forms of cancer, chronic obstructive pulmonary disease (COPD), dementia, and many other maladies.

With the goal of representing common denominators of aging in different organisms, in 2013 researchers described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account.

As a checklist of diverse major foci of current aging research, the hallmarks of aging has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not.

A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

Proteins within living cells can be modified with the addition of small chemical groups that coax the proteins to change their shape or function. Among those modifications is O-GlcNAcylation, the addition of the sugar molecule O-GlcNAc (O-linked N-acetylglucosamine). The modification is controlled by two other molecules: O-GlcNAc transferase (OGT), an enzyme that adds the sugars to proteins, and O-GlcNAcase (OGA), an enzyme that facilitates their removal. Researchers have long known that proteins in the cells of people with heart failure have more O-GlcNAc than usual. But whether increased levels of the sugar were a cause or consequence of heart failure - or an attempt by the body to ward off heart failure - has been unclear.

Researchers genetically engineered mice with higher than usual levels of OGT or OGA in heart muscle cells. The animals with high OGT - and therefore more O-GlcNAc in these cells - developed severe heart failure. Their hearts began to weaken and pump less blood at just 6 weeks old. By 25 weeks of age, more than half of all mice with high OGT had died, while no control animals with normal levels of OGT had died. "These mice developed really stunning heart failure. Similar to many patients with cardiomyopathy, the mice developed enlarged hearts, abnormal electrical rhythms and died very early."

Animals with high OGA - and therefore lower than usual O-GlcNAc in their heart cells - remained healthy, however, and showed no signs of heart failure, even when challenged with an operation that constricts one of the heart's blood vessels. To test whether high levels of O-GlcNAc could be reversed to help prevent end-stage heart failure, the researchers next cross-bred the two strains of mice, engineering animals to have both high OGT and OGA levels. These animals no longer developed heart failure or died early, presumably because while OGT led them to add excessive O-GlcNAc sugars to proteins in the heart cells, the high levels of OGA reversed that excessive modification.

Age-associated accumulation of molecular and cellular damage leads to an increased susceptibility to loss of function, disease, and death. Aging is the major risk factor for many chronic and fatal human diseases, including Alzheimer's disease, multiple cancers, cardiovascular diseases, and type 2 diabetes mellitus (T2DM), which are collectively known as age-related diseases (ARDs). However, genetic, environmental, and pharmacological interventions can ameliorate loss of function during aging and confer resistance to multiple age-related diseases in laboratory animals. Age-related multimorbidity, the presence of more than one ARD in an individual, is posing a major and increasing challenge to health care systems worldwide. An important, open question, therefore, is whether mechanisms of aging in humans contribute to multimorbidity in patients, and hence whether intervention into these mechanisms could prevent or treat more than one ARD simultaneously.

Specific biological mechanisms begin to fail as an individual ages. Individual aging hallmarks are present in the development or disordered physiology of specific ARDs. For example, loss of proteostasis appears to have a prominent role in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, which are associated with protein aggregates composed of amyloid-beta and α-synuclein, respectively.

The role of genes in individual human ARDs and ARD multimorbidity has been studied extensively, as has the link between aging hallmarks and individual ARDs. For example, previous studies have demonstrated that multiple, individual human ARDs share gene ontology (GO) terms linked to mechanisms of aging, specifically aging hallmarks. However, whether these underlying mechanisms of aging contribute to the occurrence of multimorbidity in patients has not previously been investigated. Here, we explore the notion that the same aging hallmark may contribute to risk of multiple ARDs and, therefore, results in their co-occurrence in the same individual (i.e., ARD multimorbidity).

To address this question, we text mined 917,645 literature abstracts followed by manual curation, and found strong, non-random associations between age-related diseases and aging mechanisms, confirmed by gene set enrichment analysis of genome-wide association study data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients.

An enduring challenge for bioengineering researchers is the failure of the heart to regenerate muscle tissue after a heart attack has killed part of its muscle wall. That dead tissue can strain the surrounding muscle, leading to a lethal heart enlargement. Heart experts thus have sought to create new tissue - applying a patch of heart muscle cells or injecting heart cells - to replace damaged muscle. Similarly, they have tried to stimulate division of existing heart muscle cells near the damaged area.

After an experimentally induced heart attack in a pig model, heart tissue around the infarction site was injected with about 30 million bioengineered human cardiomyocytes that were differentiated from induced pluripotent stem cells. These cells also overexpress cyclin D2, part of a family of proteins involved in cell division. Compared to control human cardiomyocytes, the cyclin D2-cardiomyocytes showed enhanced potency to repair the heart. They proliferated after injection, and by four weeks, the hearts had less pathogenic enlargement, reduced size of dead muscle tissue and improved heart function.

Intriguingly, the cyclin D2-cardiomyocytes stimulated not only their own proliferation, but also proliferation of existing heart muscle cells around the infarction site of the pig heart, as well as showing angiogenesis, the development of new blood vessels. This ability of the graft cyclin D2-cardiomyocytes to stimulate the proliferation of nearby existing heart cells suggested paracrine signaling, a type of cellular communication where a cell produces a signal that induces changes in nearby cells.