Fight Aging! Newsletter, April 22nd 2024

Aging and senescence are characterized by pervasive transcriptional dysfunction, including increased expression of transposons and introns. Our aim was to elucidate mechanisms behind this increased expression. Most transposons are found within genes and introns, with a large minority being close to genes. This raises the possibility that transcriptional readthrough and intron retention are responsible for age-related changes in transposon expression rather than expression of autonomous transposons.

To test this, we compiled public RNA-seq datasets from aged human fibroblasts, replicative and drug-induced senescence in human cells, and RNA-seq from aging mice and senescent mouse cells. Indeed, our reanalysis revealed a correlation between transposons expression, intron retention, and transcriptional readthrough across samples and within samples. Both intron retention and readthrough increased with aging or cellular senescence and these transcriptional defects were more pronounced in human samples as compared to those of mice.

In support of a causal connection between readthrough and transposon expression, analysis of models showing induced transcriptional readthrough confirmed that they also show elevated transposon expression. Taken together, our data suggest that elevated transposon reads during aging seen in various RNA-seq dataset are concomitant with multiple transcriptional defects. Intron retention and transcriptional readthrough are the most likely explanation for the expression of transposable elements that lack a functional promoter.

Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear. We aimed to clarify the longitudinal taurine intake association with fitness changes.

Participants comprised men and women aged ≥40 years who participated in the third (2002-2004; Baseline) and seventh (2010-2012; Follow-up) waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) and completed a 3-day dietary weights recording survey at baseline. A table of taurine content was prepared for 751 foods (including five food groups: Seaweed; Fish and shellfish; Meat; Eggs; and Milk and dairy products) from the Standard Tables of Food Composition in Japan (1,878 foods) 2010. Four physical fitness items (knee extension muscle strength, sit-and-reach, one-leg standing with eyes closed, and maximum walking speed) were measured at baseline and follow-up. We analyzed the association of taurine intake with physical fitness change, employing a general linear model (GLM) and trend tests for baseline taurine intake and follow-up fitness change. Adjustments included baseline variables: sex, age, height, weight, educational level, self-rated health, smoking status, depressive symptoms, and clinical history.

The estimated average daily taurine intake was 207.5 ± 145.6 mg/day at the baseline. When examining the association with the four physical fitness parameters, higher taurine intake positively increased the change in knee extension muscle strength and reduced the decline in knee extension muscle strength in the subgroup analysis of participants aged ≥65 years. No relationship was found between taurine intake and the remaining three fitness factors.

A tremendous variety of life history strategies have evolved across the animal kingdom, including some animals that achieve remarkably long lifespans (on the order of centuries) without the physiological decline that typically accompanies aging. This phenomenon, referred to as negligible senescence, is characterized by a lack of increased mortality rate or decreased fecundity as an organism ages, in combination with maintenance of physiological function and disease resistance. Animals with extraordinary longevity and negligible senescence rely on unique mechanisms to promote long-term maintenance of tissue homeostasis and physiological function while avoiding degenerative and neoplastic diseases. Understanding these mechanisms can reveal effective strategies to achieve longevity and healthy aging.

Comparative genomics between long-lived and short-lived species is a powerful approach to understand the evolution of longevity and enables unbiased discovery of genes and pathways that regulate lifespan. This approach has been used to identify molecular signatures related to longevity and has uncovered both shared and distinct strategies to modulate aging and disease resistance. Sea urchins represent a promising group of organisms to advance our understanding of lifespan determination and healthy aging. There are approximately 1,000 extant sea urchin species that exhibit a wide range of lifespans, including species with exceptional longevity and negligible senescence.

Life history data indicates that the red sea urchin, Mesocentrotus franciscanus, is one of the Earth's longest-living animals. It is reported to live more than 100 years and shows negligible senescence as defined by indeterminate growth, life-long reproduction, and no age-associated increase in mortality rate or increased incidence of disease, including no known cases of cancer. Negligible senescence has also been reported for other sea urchin species despite a wide range of lifespans. This includes the variegated sea urchin, Lytechinus variegatus, which is reported to live 3-4 years, the painted sea urchin, Lytechinus pictus, reported to live 5-7 years, and the purple sea urchin, Strongylocentrotus purpuratus, reported to live longer than 50 years.

Studies to date, conducted within the framework of known theories of aging, have demonstrated that both short-lived and long-lived sea urchin species lack many hallmarks of aging. Sea urchins maintain telomere length, antioxidant and proteasome enzyme activities, and regenerative capacity, and exhibit little accumulation of oxidative cellular damage with age. Gene expression studies using tissues of long-lived species indicate that key cellular pathways involved in protein homeostasis, tissue regeneration, and neurological function are maintained with age. Although genomes have been assembled for several sea urchin species, including S. purpuratus, L. variegatus, and L. pictus, to date no high-quality genome has become available for the long-lived red sea urchin M. franciscanus. Here we report a chromosome-level assembly for the red sea urchin genome. Targeted analysis of this genome and comparisons between long- and short-lived species sheds light on the molecular, cellular, and systemic mechanisms that promote longevity and negligible senescence.

Cellular senescence is originally defined as the irreversible loss of proliferative potential in somatic cells, which enter a viable and metabolically active state of permanent growth arrest that is distinct from quiescence and terminal differentiation. Accumulation of senescent cells contributes to age-related tissue degeneration by developing a complex senescence-associated secretory phenotype (SASP). By secreting a plethora of factors, including pro-inflammatory cytokines, chemokines, growth modulators, matrix metalloproteinases, and compromised extracellular vesicles which represent senescence-associated phenotype, senescent cells reprogram the surrounding microenvironment and cause tissue damage, thus promoting ageing and the development of age-associated diseases.

Intervention experiments have proven that senescent cell accumulation is an important driver of age-associated functional decline, multi-morbidity, and mortality, while systemic clearance of senescent cells delays ageing and extend lifespan. Therapeutically targeting cellular senescence, known as senotherapy, to eliminate senescent cells or induce senolysis, represents a rapidly growing and promising strategy for the prevention and/or treatment of ageing-related diseases. Targeting senescent cells can improve both health-span and life-span in mice.

Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases.

Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific targets for therapeutic development of senolytic drugs.

While most aging people don't suffer clinically-diagnosable Parkinson's, it's unsettlingly common to be afflicted by what are called "mild parkinsonian signs" or "Parkinsonism:" about one in six people ages 65 to 74, nearly one-third of those 75 to 84, and over half of those 85 and older. In addition to having to live with less severe versions of many common symptoms of Parkinson's itself (see below), people with Parkinsonism are at roughly double the risk of death in any given year as people the same age without it. Scientists have made exciting progress against Alzheimer's disease recently, with two new AmyloSENS therapies having proven themselves in clinical trials and more benefits and insights continuing to roll in. So it's a good time to take stock of where we are with cellular and molecular aging damage-repair therapies that would prevent and reverse the second most common neurodegenerative aging disorder.

The most visible symptoms of Parkinson's, and the ones on whose basis people are diagnosed with the "disease," are what are called the "motor symptoms." These symptoms result from the progressive loss of - and damage to - a specific population of neurons located in an area of the brain called the substantia nigra pars compacta (SNc). There is enough built-in redundancy in the SNc that we continue losing these "dopaminergic" neurons for decades without any obvious problems. But once our supply of these neurons dwindles to beneath the "threshold of pathology," we can no longer make these fine adjustments to the movement-control signals, and the motor symptoms of Parkinson's subvert the movement of our faces, hands, and bodies. The rejuvenation biotechnology solution to this problem is to repair the damage by replacing the lost neurons. The good news is that scientists have been working on dopaminergic neuron transplantation for longer than any other kind of true cell replacement (RepleniSENS) therapy. BlueRock Therapeutics uses proprietary bioprocessing to create stable master cell banks of what they call "universal iPSCs," which they have found to be compatible with the immune system of any patient. BlueRock scientists then differentiate these cells into dopaminergic neurons for transplant into the brains of people with Parkinson's. They recently reported positive safety results from a Phase I trial.

Our brains accumulate aggregates comprised of the protein alpha-synuclein (AS) as we age, both inside and between our neurons. People suffering from diagnosed Parkinson's and closely-related neurological aging disorders bear especially high burdens of these aggregates. Fortunately, researchers are currently running clinical trials to test numerous AmyloSENS therapies to clear AS aggregates located outside of cells. Most of these trials are in Phase II. Unfortunately, no one has yet developed LysoSENS therapies to target AS aggregates inside the cell, and it's these intracellular AS aggregates that likely inflict the greatest harm. The main reason for this seemingly backward prioritization is that it's not obvious how you would target AS aggregates inside cells. Fortunately, there is a potential path forward. Several years ago, researchers reported on a novel way to smuggle antibodies into cells intact. If researchers could instead send in catalytic antibodies (catabodies) that would chop pathological aggregates into tiny pieces inside the cell. SENS Research Foundation scientists are working to develop this intracellular aggregate-targeting catabody approach right now.

As we age, a small percentage of long-lived cells that don't divide (such as neurons and muscle cells) get completely taken over by mitochondria that have suffered the loss of huge chunks of their DNA. And of all the cells in the body, the cell type that is most susceptible to this hostile takeover is the critical population of dopaminergic neurons whose loss is central to Parkinson's. It's not clear what the connection is between these DNA deletion-bearing mitochondria and the loss of dopaminergic neurons with age, but it seems safe to assume that even if they don't kill their host neurons, deletion-bearing mitochondria sweeping across the cell leads to an energetic brownout that makes any surviving neurons less effective. The MitoSENS lab at SENS Research Foundation is working to develop three different platform technologies (including the original MitoSENS strategy of allotopic expression) to prevent, replace, or bypass mitochondrial DNA mutations.

Astrocytes are a kind of cellular butler for brain neurons, serving them energy sources and keeping their environment orderly so they can do their job. But like many cell types, astrocytes can turn senescent with age in response to many kinds of stress and injury. Researchers have reported that the brains of people with Parkinson's have a higher burden of senescent astrocytes than do people the same age who are free of the disease. To see if senescent astrocytes were really driving Parkinson's-like degeneration in living mammals, the researchers conducted an experiment using mice in whom they could destroy senescent cells at will. Scientists had engineered these mice with ApoptoSENS "suicide genes" that would detonate in senescent cells anytime the scientists "pulled the trigger" by treating them with a drug that activates the genetic system. They treated one group of these Parkinson's-like mice with the drug that would activate the ApoptoSENS "suicide genes" in any senescent cells they might harbor, while leaving another group of Parkinson's mice untreated for comparison. The control Parkinson's mice suffered a massive loss of dopaminergic neurons, developed movement problems that stand in for the symptoms of Parkinson's, and lost much of their ability to generate new neurons elsewhere in the brain. But much of this damage and dysfunction was prevented when researchers gave Parkinson's mice an ApoptoSENS treatment.

Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of Alzheimer's disease (AD), possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging. To shed light into this question, serum anti-HSV IgG levels were correlated with measures of Aβ deposits and blood markers of neurodegeneration in cognitively normal older adults. Additionally, we investigated whether associations between anti-HSV IgG and AD markers were more evident in APOE4 carriers.

We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration.

These results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.

A decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration. Mesenchymal stem cells (MSCs) treating thymic ageing is a promising strategy. Aged rhesus monkeys were treated with MSCs to establish a thymic senescence model, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and ELISA were performed to observe the structure and function of the thymus. TEC aging model and MSCs co-culture system were established to detect DNA methylation modification and transcriptomic changes, correlation analysis between transcription factor methylation and mRNA expression, and q-PCR, immunofluorescence staining, and Western blot were used to identified key genes.

MSCs improved the structure and function of the thymus in elderly macaque monkeys; reduced the expression levels of β-Gal, P16, and P21; and increased the activity of aging TECs. There were 501 genes with increased methylation in the promoter region in the treated group compared with the untreated group, among which 23 genes were involved in the negative regulation of cell growth, proliferation, and apoptosis, while 591 genes had decreased methylation, among which 37 genes were associated with promoting cell growth and proliferation and inhibiting apoptosis. Furthermore, 66 genes showed a negative correlation between promoter methylation levels and gene transcription; specifically, PDE5A, DUOX2, LAMP1, and SVIL were downregulated with increased methylation, inhibiting growth and development, while POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1, and TRIM3 were upregulated with decreased methylation, promoting cell growth.

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. As the first-responder to the pathogens and damage in the immune response, macrophages play a vital role in the function of phagocytosis and polarization towards different situations to mediate the inflammation inside individuals. Senescent macrophages are usually featured with an unbalanced polarization state, compromised phagocytosis, impaired migration, and damaged autophagy. Due to the abnormal accumulation and the aberrant functions of senescent macrophages, aged people tend to be unhealthy or with acerbated diseases.

Senescent macrophages play various functions in different diseases or organs which indicates that treatments should be specialized for the distinctive characteristics of senescent macrophages. In the cognitive decline, senescent macrophages turn to behave abnormally in phagocytosis for the dampened scavenging of abnormal unfolded proteins in the central nervous system. The imbalanced polarization state in senescent macrophages also contributes to the development of malignant cancers. More senescent macrophages tend to the M2 phenotype promoting tumor cells proliferating and counteract against cytotoxic T lymphocytes.

Contrarily, in ovarian tissue, senescent macrophages turn to the M1 phenotype with a higher level of iNOS which causes ovarian aging. Secretions of senescent macrophages are also in close relationship with some organ disorders. Grancalcin produced by senescent macrophages would exacerbate skeletal aging for the impaired balance between osteogenesis and adipogenesis of bone marrow stroma cells. Additionally, metabolic disturbances like chaotic cholesterol levels in senescent macrophages cause age-related macular degeneration for their proangiogenic function.

Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase health span, remain unknown. We demonstrate that the activity of a spatially defined neuronal population in the anterior and ventral portions of the medial and lateral preoptic area (avMLPA), which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor like state (TLS) in mice.

Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves health span. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the pro-longevity effect of torpor-like states is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the pro-longevity effects of torpor and hibernation and support the growing body of evidence that Tb is an important mediator of aging processes.

Mitochondrial dysfunction critically contributes to many major human diseases. The impact of specific gut microbial metabolites on mitochondrial functions of animals and the underlying mechanisms remain to be uncovered. Here, we report a profound role of bacterial peptidoglycan muropeptides in promoting mitochondrial functions in multiple mammalian models. Muropeptide addition to human intestinal epithelial cells (IECs) leads to increased oxidative respiration and ATP production and decreased oxidative stress. Strikingly, muropeptide treatment can recover mitochondrial structure and functions and inhibits several pathological phenotypes of fibroblast cells derived from patients with mitochondrial disease.

In mice, muropeptides accumulate in mitochondria of IECs and promote small intestinal homeostasis and nutrient absorption by modulating energy metabolism. Muropeptides directly bind to ATP synthase, stabilize the complex, and promote its enzymatic activity in vitro, supporting the hypothesis that muropeptides promote mitochondria homeostasis at least in part by acting as ATP synthase agonists. This study reveals a potential treatment for human mitochondrial diseases.

The present study assessed cognitive test performance in English older adults in relation to long-term air pollution exposure at the residential address. The follow-up period of 15 years and the large number of repeated measurements make the present study unique in terms of design and data availability. Increasing exposure to NO2, PM10 and PM2.5 was consistently found to be associated with decreased memory and executive function test performance, whilst ozone showed the opposite effect. The results remained similar in the analysis including residents of London only, for whom exposure to NO2 and PM was higher. As an illustrative example, the decline in memory and executive function scores per interquartile range (IQR) increase in long-term NO2 exposure was found equivalent to ageing by about 1.5 and 4 years respectively.

In order to fully elucidate the potentially adverse cognitive effects of air pollution, further study into the underlying biological pathways and mechanisms through which air pollution may contribute to cognitive decline is required alongside the expanding epidemiological work. Translocation of inhaled particles from the lung to the brain via the bloodstream provides one possible pathway through which particulate matter may affect cognition, as well as inhalation through the nose and transportation to the olfactory bulb via olfactory nerves. Evidence for such pathways is currently limited and further experimental studies are required.

To date, we have used our Cholesterol Degrading Platform (CDP) to demonstrate rapid and profound reversal of disease in mouse models of (a) metabolic dysfunction-associated steatohepatitis (MASH), a progression of fatty liver towards liver failure that is characterized by fibrosis and loss of liver function, (b) atherosclerosis, the buildup of fatty plaques in blood vessel walls, leading to cardiovascular disease and stroke, and (c) homozygous familial hypercholesterolemia (HoFH), an inherited condition involving loss-of-function mutations in low-density lipoprotein receptors (LDLR) that causes high blood cholesterol and greatly accelerated atherosclerosis.

These three conditions are characterized by being largely irreversible under the present standards of care. While slowing the progression of disease is sometimes possible, few patients have been shown to achieve any meaningful reversal of established liver fibrosis or arterial atherosclerotic plaque, and the methods used to treat those patients are not consistently effective in other patients.

In each case, 6 to 8 weeks of once-weekly injections of CDP therapy produced sizable improvements in blood chemistry, including reductions in alanine aminotransferase (ALT), a measure of liver cell death and stress, and in histological assessments of disease. In MASH model mice, a 52% reduction in liver fibrosis was observed versus untreated controls. In the ApoE-knockout mouse model of atherosclerosis, plaque lipids were reduced by 19% while plaque collagen increased by 23% versus controls, a dramatic stabilization of unstable plaques at risk of rupture. In the LDLR-knockout mouse model of HoFH, plaque cross-sectional area decreased by 17% and mouse treadmill performance improved by 60% versus controls, a considerable improvement in cardiovascular function.

To compare this with other present efforts, the drug, resmetirom (Madrigal Pharmaceuticals), recently approved by the FDA for the treatment of MASH, has no effect on fibrosis in mice over 8 weeks of treatment. In the MAESTRO human trial in patients with comparatively mild MASH, the treated groups saw only a 25% reduction in fibrosis compared to 14% in the placebo group after 52 weeks of treatment. In the case of atherosclerosis, large clinical trials have shown that long-term treatment with statins or other low-density lipoprotein (LDL)-lowering technologies such as PCSK9 inhibitors fails to produce a reduction in atherosclerotic plaque volume of more than a few percentage points. Our CDP therapy far outperforms these approaches to treatment.

Perhaps the most interesting outcome is that we have demonstrated that a localized excess of free cholesterol is indeed a major factor in many conditions, age-related and obesity-related. It had been theorized that this was the case for liver diseases such as MASH, but lacking a technology that selectively cleared only free cholesterol, this had to remain only a compelling theory. Armed with that selective clearance technology, our results have now convincingly demonstrated that free cholesterol toxicity is a major, important target for many conditions.

Longevity and resilience are two fundamental traits for more sustainable livestock production. These traits are closely related, as resilient animals tend to have longer lifespans. An interesting criterion for increasing longevity in rabbits could be based on the information provided by its gut microbiome. The gut microbiome is essential for regulating health and plays crucial roles in the development of the immune system.

The aim of this research was to investigate if animals with different longevities have different microbial profiles. We sequenced the 16S rRNA gene from soft faeces from 95 does. First, we compared two maternal rabbit lines with different longevities; a standard longevity maternal line (A) and a maternal line (LP) that was founded based on longevity criteria: females with a minimum of 25 parities with an average prolificacy per parity of 9 or more. Second, we compared the gut microbiota of two groups of animals from line LP with different longevities: females that died/were culled with two parities or less (LLP) and females with more than 15 parities (HLP).

Differences in alpha diversity and beta diversity were observed between lines A and LP, and analysis showed a high prediction accuracy (more than 91%) of classification of animals to line A versus LP. Interestingly, some of the most important microbial taxa identified were common to both comparisons (Akkermansia, Christensenellaceae R-7, Uncultured Eubacteriaceae, among others) and have been reported to be related to resilience and longevity.

In summary, our results indicate that the first parity gut microbiome profile differs between the two rabbit maternal lines (A and LP) and, to a lesser extent, between animals of line LP with different longevities (LLP and HLP). Several genera were able to discriminate animals from the two lines and animals with different longevities, which shows that the gut microbiome could be used as a predictive factor for longevity, or as a selection criterion for these traits.

The process by which lung injury either leads to healing or fibrosis relies in part on what happens to a cell called a fibroblast, which forms connective tissue. During injury or illness, fibroblasts are activated, becoming myofibroblasts that form scar tissue by secreting collagen. When the job is done, these fibroblasts must be deactivated, or de-differentiated, to go back to their quiet state or undergo programmed cell death and be cleared.

This is the major distinction between normal wound healing and fibrosis - the persistence of activated myofibroblasts. That deactivation is controlled by molecular brakes. The study examined one of these brakes, called MKP1 - which researchers found was expressed at lower levels in fibroblasts from patients with idiopathic pulmonary fibrosis. By genetically eliminating MKP1 in fibroblasts of mice after establishing lung injury, the researchers saw that fibrosis continued uncontrolled.

"Instead of at day 63, seeing that nice resolution, you still see fibrosis. We argued by contradiction: when you knock out this brake, fibrosis that would otherwise naturally disappear, persists and therefore MKP1 is necessary for spontaneous resolution of fibrosis. We demonstrated that neither of the FDA approved drugs for lung fibrosis, pirfenidone and nintedanib, are able to turn off myofibroblasts. That's totally in keeping with the fact that they do slow the progression, but they don't halt or reverse disease."

In recent years, laboratory research has shown that we may be able to counteract age-related diseases by intervening in the fundamental processes that lead to ageing. Although science has increasingly mapped out how metabolism changes during aging, large parts remained uncharted. "We wanted to add a new chapter to the atlas. Lipids are an important part of our diet, and crucial for the functioning of our body cells. Specific lipids make up the membrane of cells, which ensures that the inside and outside remain separate."

In order to add this new chapter, the research team investigated how the composition of fats changes in mice. They looked at ten different tissues, including muscles, kidneys, liver and heart. It was noticed that one type of lipid, the bis(monoacylglycero)phosphates (or BMPs), were elevated in all tissues from the older animals. Suggesting an accumulation of these lipids during aging. They then investigated whether this also happens in humans. Although it was not possible to obtain as many different tissues, the accumulation of BMP was also visible in muscle biopsies of older people. Finally, they then completed more muscle biopsies from people before and after a healthy intervention that included one hour of exercise a day and saw the level of BMPs decreased in the active participants.