An Example of Present Work on Improving Vitrification
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Interest in developing means of reversible vitrification for tissue preservation has been growing outside the cryonics community in recent years. This is a good thing for cryonics as an industry, as a greater interest in reversible tissue preservation in the broader research community will lead to both technological improvements that can be used by cryonics providers and a greater acceptance of cryonics. Cryonics is a legitimate approach to medical intervention where there is no other option for the patient, but despite greater public support for cryonics from scientists, there remains considerable and unfounded hostility within some portions of the research community. Hopefully this will change in the years ahead with meaningful progress towards the broader use of vitrification:

Researchers have discovered a new approach to "vitrification," or ice-free cryopreservation, that could ultimately allow a much wider use of extreme cold to preserve tissues and even organs for later use. Cryopreservation has already found widespread use in simpler applications such as preserving semen, blood, embryos, plant seeds and some other biological applications. But it is often constrained by the crystallization that occurs when water freezes, which can damage or destroy tissues and cells. To address this, researchers have used various types of cryoprotectants that help reduce cell damage during the freezing process - among them is ethylene glycol, literally the same compound often used in automobile radiators to prevent freezing. A problem is that many of these cryoprotectants are toxic, and can damage or kill the very cells they are trying to protect from the forces of extreme cold.

In the new research, the engineers developed a mathematical model to simulate the freezing process in the presence of cryoprotectants, and identified a way to minimize damage. They found that if cells are initially exposed to a low concentration of cryoprotectant and time is allowed for the cells to swell, then the sample can be vitrified after rapidly adding a high concentration of cryoprotectants. The end result is much less overall toxicity. The research showed that healthy cell survival following vitrification rose from about 10 percent with a conventional approach to more than 80 percent with the new optimized procedure. "The biggest single problem and limiting factor in vitrification is cryoprotectant toxicity, and this helps to address that. The model should also help us identify less toxic cryoprotectants, and ultimately open the door to vitrification of more complex tissues and perhaps complete organs."

If that were possible, many more applications of vitrification could be feasible, especially as future progress is made in the rapidly advancing field of tissue regeneration, in which stem cells can be used to grow new tissues or even organs. Tissues could be made in small amounts and then stored until needed for transplantation. Organs being used for transplants could be routinely preserved until a precise immunological match was found for their use. Conceptually, a person could even grow a spare heart or liver from their own stem cells and preserve it through vitrification in case it was ever needed.


Cytomegalovirus Impairs the Immune Response to Exercise
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Here researchers provide evidence for one of the many detrimental consequences of cytomegalovirus (CMV) infection. CMV is a near ubiquitous persistent herpesvirus, present in the majority of the population by the time they reach old age. It is thought responsible for some fraction of the age-related disarray of the immune system, as it cannot be cleared and its presence over the years causes ever more memory cells to be uselessly specialized to track it, leaving ever less room for immune cells capable of taking action. One possible approach to this issue is to destroy the excess memory cells to free up space, possibly coupled with delivering new immune cells via cell therapy, but there is little work taking place on that front, as is true of most potential rejuvenation treatments.

The rapid redeployment of natural killer (NK) cells between the tissues and the peripheral circulation is an archetypal feature of the acute stress response. The response can be evoked using acute bouts of dynamic exercise and is often considered to be an accurate representation of an organism's ability to mount an effective immune response during fight-or-flight scenarios when tissue injury and infection are likely to occur. Acute exercise is associated with increased levels of stress hormones which interact with β-adrenergic receptors (β-AR) on the surface of lymphocytes. NK-cells express more β-AR than other lymphocytes and, as a result, they are the most responsive lymphocyte subset to exercise.

Cytomegalovirus (CMV) is a prevalent beta herpesvirus infecting 50-80% of the US population. We have shown that prior exposure to CMV profoundly impacts the redistribution of lymphocytes to an acute exercise bout. While those with CMV have an augmented redeployment of CD8+ T-cells and γδ T-cells, NK-cell mobilization is dramatically impaired. This blunted NK-cell response appears to be attributable to a CMV-induced accumulation of specific NK-cell subsets that have a lower expression of β2-AR and an impaired ability to produce cyclic AMP in response to in vitro stimulation with the β-agonist isoproterenol. Moreover, those with CMV fail to exhibit exercise-induced enhancements in NK-cell function, indicating that CMV may compromise NK-cell mediated immunosurveillance after an acute bout of strenuous exercise.

In addition to infection history, aging is known to have a profound impact on the cellular response to acute stress and exercise; however, studies investigating the effects of aging on NK-cell exercise responsiveness are lacking. While aging has been reported in some studies to have no effect on NK-cell mobilization with exercise, several of the phenotypic hallmarks of aging overlap with those associated with latent CMV infection in the young. Despite CMV prevalence increasing with age, previous studies have compared NK-cell responses between young and old exercisers without accounting for this confounding variable. We showed recently that CMV was associated with enhanced redeployment of CD8+ T-cells regardless of age, while, conversely, aging impairs the redeployment of γδ T-cells independently of CMV. However, no study to our knowledge has compared NK-cell responses to a single bout of exercise between different age groups while controlling for CMV status. Given that CMV prevalence increases with age and many of the effects of CMV mirror those attributable to aging, it is important to resolve the effects of age and CMV infection on the frequency and exercise responsiveness of distinct NK-cell subsets.

The aim of this study was to determine if latent CMV infection blunts the redeployment of NK-cells to a single exercise bout in older individuals as it does in the young and to delineate the effects of age and CMV on the redeployment of discrete NK-cell subsets. We show here that CMV has a potent blunting effect on exercise-induced NK-cell mobilization in both younger (23-39 yrs) and older (50-64 yrs) subjects with the greatest mobilization being seen in the CMV-negative older group.


Nrf2 in Aging and Longevity
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The transcription factor nrf2 regulates levels of antioxidant proteins, a part of the response to everyday cellular stress, such as that induced by raised mitochondrial activity and greater generation of reactive oxygen species (ROS) during exercise. Greater nrf2 activity shows up in long-lived species and in the modest slowing of aging that can be achieved via hormesis in some species. Here is an open access review paper on this topic:

The role of Nrf2 in responding to cytotoxic stressors is well defined. However, only within the last few years have studies elucidated how Nrf2 function changes with age and how changes in Nrf2 activity contribute to the aging phenotype. Aged mice show similar losses in cellular redox capacity to those observed in Nrf2 knockout mice, suggesting that Nrf2 dysregulation with age may be responsible for the loss of cellular redox status. Diminished Nrf2 target gene expression with age is accompanied by increased muscle ROS production, glutathione depletion, and increased oxidant damage to proteins, DNA, and lipids in both humans and rodents. Therefore, given that Nrf2 activity decreases with age alongside increased oxidant stress, interventions that activate Nrf2 may impact the aging process and longevity.

Support for the role of Nrf2 in regulation of lifespan comes from Nrf2 gain of function and loss of function studies. For example, experimental deletion of the antielectrophilic gene glutathione transferase (gGsta4) activated Nrf2 and significantly extended lifespan in mice. This mutation increased electrophilic lipid peroxidation products and increased nuclear Nrf2 activity by 43% and 38% in liver and skeletal muscle, respectively. The authors propose that deletion of this glutathione transferase gene resulted in chronic moderate Nrf2 activation and presumably elevated downstream Nrf2 signaling throughout the mouse lifespan. Studies of the Nrf2 homolog SKN-1 in Caenorhabditis elegans (C. elegans) further suggest that Nrf2 may be implicated in longevity processes. Upon activation, SKN-1 upregulates genes involved in the oxidative stress response, including many orthologs to those regulated by mammalian Nrf2. Similar to mouse Nrf2 knockouts, SKN-1 mutants show diminished resistance to oxidative stress and shortened lifespan. On the other hand, moderate overexpression of a constitutively active SKN-1 increases lifespan, alongside increased resistance to oxidative stress.

The naked mole rat is an exceptionally long-lived species, with a lifespan four times longer than similarly sized rodents, thus making the naked mole rat an important model for longevity studies. Naked mole rats do not have typical lifespan curves in which mortality rates increase with age, but rather they experience few of the biological changes typically associated with aging. Naked mole rats also have significantly elevated proteasome quality control mechanisms. The high breakdown and clearance of damaged proteins is suspected to be largely due to increased Nrf2 expression. In support of the hypothesized role of Nrf2 in naked mole rat longevity, under nonstressed conditions, naked mole rats have greater protein levels of Nrf2 and greater expression of Nrf2-regulated enzymes in fibroblasts and liver. These data suggest Nrf2 may be responsible for the heightened quality control mechanisms in naked mole rats and may be associated with their exceptional longevity.


A Mechanism By Which Amyloid-β Attacks Synapses
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Researchers here provide evidence for a fairly direct link between the growing levels of amyloid-β associated with Alzheimer's disease and the loss of synapses characteristic of the condition. Since the mechanism is so direct, success in present efforts to clear amyloid-β from the brain, such as via immunotherapy, should also minimize this part of the pathology of Alzheimer's disease:

"One of the first signs of Alzheimer's disease is the loss of synapses - the structures that connect neurons in the brain. Synapses are required for all brain functions, and particularly for learning and forming memories. In Alzheimer's disease, this loss of synapses occurs very early on, when people still only have mild cognitive impairment, and long before the nerve cells themselves die. We have identified a new molecular mechanism which directly contributes to this synapse loss - a discovery we hope could eventually lead to earlier diagnosis of the disease and new treatments."

The team studied a protein in the brain called neural cell adhesion molecule 2, or NCAM2 - one of a family of molecules that physically connects the membranes of synapses and help stabilise these long lasting synaptic contacts between neurons. Using post-mortem brain tissue from people with and without the condition, they discovered that synaptic NCAM2 levels in the part of the brain known as the hippocampus were low in those with Alzheimer's disease. They also showed in mice studies and in the laboratory that NCAM2 was broken down by another protein called beta-amyloid, which is the main component of the plaques that build up in the brains of people with the disease. "Our research shows the loss of synapses is linked to the loss of NCAM2 as a result of the toxic effects of beta-amyloid. It opens up a new avenue for research on possible treatments that can prevent the destruction of NCAM2 in the brain."


An Interesting Opinion on Metformin
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The evidence for metformin to slightly slow the aging process is all over the map. It is sketchy and contradictory in comparison to the robust results from rapamycin, for example. This isn't preventing a coalition of researchers from pushing forward on a clinical trial with the FDA, but I suspect that trial is much more a means of changing the FDA position on treatments for aging, which are currently not permitted, than an attempt to show results from metformin. Metformin is useful there because it is an established drug with a much lower set of regulatory barriers for reuse in other contexts, making it harder for regulators to throw roadblocks in the way of a trial to treat aging.

A researcher offers an interesting opinion on metformin in this open access paper. In his view the evidence for modestly reduced cancer rates resulting from metformin use is already good enough that, given the very low cost of the drug, it should be formally adopted and verified for cancer prevention in the general population. This is perhaps best considered in the context of the debate of two years ago over whether rapamycin extends life by reducing cancer risk or slowing aging:

During the last decade, there has been a burst of interest in the antidiabetic biguanide metformin as a candidate drug for cancer chemoprevention. Analysis of the available data has shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters in a wide range of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. It is very important to note that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides.

The history of biguanides in oncology started in the 1970s, is rather dramatic, and seems not to come to "a happy end" at the present time. The first publications in 1974-1982 showing the high potential of PF and BF in prevention of spontaneous and induced carcinogenesis were not met an interest adequate to the degree of real importance of these finding. Whereas both in vitro and in vivo experiments provide new evidence of anti-carcinogenic potential of biguanides, and the majority of clinical observations clearly demonstrates protective effect of MF in relation to many localization of cancer, there are some publications on results of clinical trials that are inconclusive and sometime were demonstrated adverse effect of MF. Recently a researcher explaining possible reasons for this inconsistency cited the rather sardonic comment of a leading scientist in the field: "The problem with metformin is it's cheap, it's widely available, it has a great safety profile, and anyone can use it". Really, it is difficult to say better... In PubMed, under the words such as "metformin and cancer" the number of indexed papers were increasing exponentially from zero in 1990 to more than 2500 last September. Among them around 185 reviews on the topic were published just in the last 5 years. There are too many works and still no final conclusion. It may be the time to make this long story short; we believe that efficacy of MF should be evaluated according to criteria, experience and rules of the WHO International Agency for Research on Cancer.


Yet More Mapping of Age-Related Epigenetic Changes
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Epigenetic changes occur constantly, altering the production of proteins in response to circumstances, and thus changing cell and tissue behavior. Some of these changes occur in reaction to the cell and tissue damage of aging, and are characteristic enough to allow development of a measure of biological age, an assessment of how damaged an individual is. This is a work in progress, but a good, cheap measure of biological age is a needed tool in the field of longevity science. Currently the only way to establish that potential rejuvenation treatment works in the sense of extending healthy life is to wait and see what it does to life expectancy, which makes exploration of ideas prohibitively expensive, and slows progress across the whole field:

To examine the changes that occur in blood as an individual ages, researchers conducted an extensive study using thousands of patient blood samples. In a remarkable show of replication, the study was initially performed with blood samples from individuals of European ancestry and then replicated in additional European ancestry samples, totaling an amazing 14,983 individual European ancestry samples. The study was then extended to various ethnic groups, including samples from individuals of Hispanic, African, or Native American ancestry. The study identified 1,497 genes in blood cells and/or brain tissue that showed significantly differential expression patterns in older individuals when compared to younger individuals.

There were three distinct groups of genes that were negatively correlated with chronological age. The first group included three subgroups: ribosomal genes (factories on which a RNA is translated into a protein), mitochondrial genes (energy factories of the cells), and genes associated with DNA replication and repair (DNA maintenance and fidelity). All of the genes associated with these subgroups are vitally important to the health of a cell and tissue. The second large group consisted of genes associated with immunity. The third large group was composed of genes that code for the actual ribosomal subunits. Decreased gene expression could help explain the decreased "health" of older cells and increased mutation rates in older cells. There were also four groups of genes positively correlated with age, which were focused on cellular structure, immunity, fatty acid metabolism, and lysosome activity.

Another interesting finding in this study involved epigenetic patterns, specifically methylation on cytosines (one of the four nucleotide bases in DNA). This study showed that those genes whose expression pattern changed with age were highly enriched for the presence of regulatory cytosines. This could indicate how gene expression is controlled as the individual ages. There are several targeted methylation therapies in development that might potentially offer the ability to effectively and safely alter these methylation patterns for therapeutic purposes. The authors found that by combining the transcriptomic expression patterns and the epigenetic patterns a "chronological" age predictor could be used to better understand an individual's "age" in terms of health. Further refinement is needed, but this type of predictor could have a substantial impact on prediction, diagnosis and treatment of individuals, perhaps even allowing for preventive treatments before symptoms progress to disease level changes.


Slowing Aging Slows Parkinson's Development, Even When Caused By Genetic Mutations
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In some patients Parkinson's disease is associated with genetic variants, most likely because those differences increase susceptibility to damage in the small but critical population of neurons that are destroyed as the disease progresses. It is all very much a matter of levels of damage, however, and so we shouldn't be surprised to see that established methods of modestly slowing aging in laboratory animals also slow the progression of Parkinson's-like model conditions created through genetic alteration. Aging, after all, is also a matter of accumulating damage - the less damage you have, the less aged, dysfunctional, and frail you are.

Scientists have shown in disease models that slowing aging reduces degeneration related to Parkinson's. "It is unknown why symptoms take many decades to develop when inherited mutations that cause the disease are present from birth. Aging is the greatest risk factor for developing Parkinson's - we believe changes that occur during the aging process make brain cells more susceptible to disease-causing mutations that don't cause issues in younger people."

In the brain, Parkinson's is marked by the dysfunction and death of the nerve cells that produce dopamine - a chemical that plays a key role in many important functions, including motor control. Clumps of a protein called alpha-synuclein also are found in brain cells of most people with Parkinson's, although scientists are still trying to pin down their exact role. As part of their search for ways to prevent the disease, researchers delayed the aging process in genetic models of Parkinson's disease. They demonstrated that slower aging imparts protection against the loss of dopamine-producing cells in the brain and decreases the formation of alpha-synuclein clumps - ­both hallmark features of Parkinson's. "This work suggests that slowing aging can have protective effects on the brain cells that otherwise may become damaged in Parkinson's. Our goal is to translate this knowledge into therapies that slow, stop or reverse disease progression."

The team used the worm Caenorhabditis elegans as a genetic model for Parkinson's. Thanks to its simple and well-mapped nervous system, and the ease of genetic manipulation and maintenance of the worm, C. elegans is well-suited for the identification of novel treatment strategies for neurodegenerative diseases. Worm models of Parkinson's disease that expressed either a mutated LRRK2 gene or a mutated alpha-synuclein gene - both of which cause Parkinson's - were crossed with a long-lived strain of the worm to create two new strains with longer lifespans. The researchers found that long-lived LRRK2 and alpha-synuclein worms lost dopamine neurons at a much slower rate than their counterparts with normal lifespans. In fact, the long-lived LRRK2 worms had more dopamine neurons left on day 30 of the study than the LRRK2 worms with a normal lifespan of three weeks had on day eight of adulthood. Slowing aging also effectively reduced motor deficits related to the loss of dopamine-producing cells and eliminated the increased sensitivity to stress shown by worms with a normal lifespan.


The Question of Whether to Build Rejuvenation Therapies
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Should we build rejuvenation therapies? Hell yes. Are we? Barely, as nowhere near enough of an effort is being made. This is an opinion piece by Aubrey de Grey of the SENS Research Foundation:

Aging is a hot topic among the chattering classes these days. What with biotech companies like Calico and Human Longevity Inc. being founded with the mission to defeat aging, and venerable institutions such as Prudential proclaiming the imminence of superlongevity on billboards, there's no denying that this is a time of great interest in our oldest and deepest-held dream - to escape from the tyranny of inexorable and ultimately fatal physiological decline.

But hang on - is the buzz around aging really reflective of what's being done to realize this goal? The briefest dispassionate analysis reveals a different story altogether. The proportion of government spending allocated in the industrialized world to diseases and disabilities of old age is appropriately high, but it is overwhelmingly dedicated to the transparently quixotic approach of attacking those ailments directly - as if they were infections - rather than attacking their lifelong accumulating causes. The latter approach is the focus of biomedical gerontology. Researchers in this field recognize that any direct attack on late-life disease is doomed to become progressively less effective as the causes of those diseases continue to accumulate, so they focus instead on those causes - the "damage" that the body inflicts on itself throughout life in the course of its everyday operation. But they comprise a tiny coterie of scientists - far too few, and with access to far too little funding, to allow progress to occur at anywhere near the maximum rate that the simple technical difficulty of the problem would allow.

I believe that the main reason for this tragic myopia is a phobia about aging so ancient and deep-seated that it overpowers the rationality of nearly all of us, even the most intelligent and educated. Aging holds us in a psychological stranglehold, preventing us from even contemplating the idea of its medical conquest. Thus it is that grown adults find it possible to argue that we should forever continue to let everyone endure the number one cause of human suffering. Unfortunately for us - by which I mean, for the whole of humanity - those adults include the overwhelming majority of the people who control enough money (whether their own, their company's or the taxpayer's) to make a difference. Even without getting into the debate about what approaches to this challenge are the most promising, one can no longer escape the fact that most biomedical gerontologists now agree that we are approaching a time of sharply accelerated progress in extending healthy lifespan. Except, of course, by letting that expert opinion go in one ear and out the other. And that, I'm afraid to say, is what most decision-makers are still doing. The marginalization of anti-aging research is our most shameful humanitarian failure.


Energy-Carrying Molecules to Boost Aging Mitochondria?
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Here I'll point out the latest in the Question of the Month series from the SENS Research Foundation, in which the staff are far more polite than I regarding the unmerited hype that seems to accompany both supplement research in general and research emerging from the Sinclair lab at Harvard in specific:

Q: In recent months, I've seen quite a lot of promotional material for a dietary supplement called nicotinamide riboside (NR). The companies involved say that Harvard researchers showed that this supplement restores mitochondrial function in the cells of aging mice, completely reversing the aging process in muscles. Some of them add that other research has shown that it improves metabolism, fights fat and obesity, and is protective of brain function. What do you think of this supplement?

A: It must be clarified that the substance used in the Harvard research was not actually NR, but another compound called nicotinamide mononucleotide (NMN). But NMN is unsuitable for oral supplementation, so the Harvard researchers injected their mice with NMN rather than giving it to them in their feed. With the excited coverage that greeted the research, supplement companies have promoted NR as a substitute, because it was already in production and can be taken orally. Because NR is a precursor to NMN, which in turn is used for the synthesis of the energy shuttle molecule nicotinamide adenine dinucleotide (NAD), many supplement vendors assert or imply that the results with NMN can also be gained with NR.

That all may sound promising, and it certainly makes for effective marketing copy. But no study has actually been done demonstrating that NR has similar effects to NMN in the muscles of otherwise-healthy aging mice. In fact, one study found that high-dose NR supplementation was unable to increase NAD+­ levels in muscle tissue or the mitochondrial fraction of normal, healthy mice. Additionally, overexpressing the gene that converts NR to NMN in these animals' muscles still didn't affect muscle mitochondrial function in the way that the Harvard researchers reported with NMN, suggesting that the effects observed with injected NMN may involve some kind of systemic response to having NMN itself circulating in the bloodstream. This casts considerable doubt on the assumption that either NR, or some other supplement that raises cellular NAD+­ levels, will replicate the effects of NMN on aging muscle. Additionally, interpretation of the Harvard report is greatly hampered by the lack of information of the animals' weight or food intake, which raises the possibility of effects mediated by calorie restriction or (contrariwise) by the simple overfeeding of all the animals in the study.

It's also important for readers of the press coverage to understand just what was involved when such stories reported that NMN treatment "reversed the effects of aging" on the mice's muscles. Readers would be forgiven for imagining the muscles of frail, elderly mice suddenly swelling to youthful size, able to perform tiny rodent bench presses with the strength and endurance of much younger animals. In reality, though, as the investigators were careful to point out in the original scientific paper, while their treated animals' muscle cells exhibited biochemical evidence of improved ("rejuvenated") metabolism and insulin-stimulated glucose uptake, "we did not observe an improvement in muscle strength." This important detail was missing from almost all of the reporting in the popular press. While it's possible, as the scientists speculate, that longer-term treatment would have led to some recovery of muscle function, the lack of any observed improvement in actual muscle strength calls into question the functional significance of the biochemical "rejuvenation" they report.


Considering the Possibility of a Type 4 Age-Related Diabetes
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Type 1 diabetes is an autoimmune disease, type 2 diabetes is a lifestyle disease largely caused by being overweight, some researchers have suggested that Alzheimer's disease is a type 3 diabetes, and here evidence is presented for the existence of a type 4 age-related diabetes:

Diabetes is often the result of obesity and poor diet choices, but for some older adults the disease might simply be a consequence of aging. New research has discovered that diabetes - or insulin resistance - in aged, lean mice has a different cellular cause than the diabetes that results from weight gain (type 2). And the findings point toward a possible cure for what the scientists are now calling a new kind of diabetes (type 4). "A lot of diabetes in the elderly goes undiagnosed because they don't have the classical risk factors for type 2 diabetes, such as obesity. We hope our discovery not only leads to therapeutics, but to an increased recognition of type 4 diabetes as a distinct disease."

Researchers set out to compare the immune systems of healthy mice, those with obesity-related diabetes and those with age-related diabetes. The mice with age-related disease, they found, had abnormally high levels of immune cells called T regulatory cells (Tregs) inside their fat tissue. Mice with obesity-related diabetes, on the other hand, had normal levels of Tregs within the tissue, despite having more fat tissue. Normally, Tregs help calm inflammation. Because fat tissue is constantly broken down and built back up as it stores and releases energy, it requires low levels of inflammation to constantly remodel itself. But as someone ages, the new research suggests, Tregs gradually accumulate within fat. And if the cells reach a tipping point where they completely block inflammation in fat tissue, they can cause fat deposits to build up inside unseen areas of the body, including the liver, leading to insulin resistance. "It was a little bit surprising since normally Tregs are supposed to be beneficial for the body."

When the scientists blocked Treg cells from accumulating in the fat by targeting a molecule that the immune cells require, mice no longer developed type 4 diabetes in old age. However, if mice became obese, blocking the Tregs in fat did not prevent type 2 insulin resistance. "It turns out that for this type of diabetes, the treatment is not losing weight. The treatment is actually losing these cells, and we show that it's possible to do that." The researchers now want to find out exactly how Tregs interact with fat tissue and whether the immune cells accumulate in other organs during normal aging. They're also planning studies to see whether the results hold true in humans. "We're working with clinicians to get samples from older, lean people with diabetes to see if this cell type is also implicated in human disease."