A blind giant tortoise lives and mates to age 194

Amazing stuff! This tortoise also survived European discoverers, explorers and seafarers stopping by at Saint Helena since 1502 AD.

"Current theory suggests that Aldabra tortoises dispersed “out of Africa,” first from the eastern African coast to Madagascar, then to Granitic Seychelles, and lastly to the Aldabra atoll, a UNESCO World Heritage Site now harboring around 100,000 tortoises ..."

"On an island in the South Atlantic Ocean, the world’s oldest known land animal spends his days munching on fresh fruit and veggies, sunbathing, napping, and getting frisky with the other members of his bisexual throuple.

At the ripe age of 194 years old, with an estimated hatching date of 1832, an Aldabra giant tortoise named Jonathan ... Old age has not come without challenges, however. Today, Jonathan is blind from cataracts and has lost his sense of smell. But the years do not appear to have diminished his libido: He still regularly mates with Emma and Frederik, two other, much younger, giant tortoises that reside with him on the island of Saint Helena.

What on Earth is Jonathan’s secret?

To find out, scientists decided to take a look at the old tortoise’s genome, as well as his epigenome—the collection of chemical changes on DNA that act like “on/off” switches for genes. ..."

From the abstract:

"Aldabra giant tortoises (Aldabrachelys gigantea) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 194-year-old Aldabra, to explore the molecular basis of his longevity.

Relative to other giant tortoises (A. gigantea and Chelonoidis abingdonii), Jonathan has unique gene variants in most aging pathways.

Moreover, Jonathan has substantial DNA methylation and methylation entropy changes compared to four other Aldabras ranging in age from a 5-year-old juvenile to older adults.

Notably, we found that lower-entropy regions in Jonathan’s methylome were enriched for the promoters of genes involved in the mitochondrial electron transport chain, and RNA metabolism. This suggests that high-fidelity transcription of the genes in these pathways may be crucial for long-lived species.

Our findings support a model for aging wherein the maintenance of low methylation entropy in gene promoters is coupled to efficient mitochondrial energy production, efficient RNA processing, and efficient genomic repair."

ScienceAdviser

Epigenetic insights into extreme longevity in the world’s oldest terrestrial animal, Jonathan

Jonathan, the tortoise

Chart of the day

In 1963, there ware just 153 centenarians, total population 96 million (Source).

In 2025, total population 123 million. Source

 

Weight-loss drug slows ageing in female mice (one inbred strain of laboratory mice). Really!

Amazing stuff! However, this was only reported for a very narrowly defined population of mice. I am not sure why Nature journal highlighted this research.

You get another chance to gain weight again! Just kidding!

"The GLP-1 medication semaglutide (Ozempic, Wegovy) has anti-ageing properties, at least in mice, write gerontologists ... Older female mice that received semaglutide lived longer than those that didn’t receive the drug, and had better outcomes for inflammation, cellular senescence, and neurodegeneration outcomes. The treated mice also performed better on cognitive tests than untreated mice fed a strict diet, suggesting the drug has benefits that aren’t explained by calorie reduction alone."

From the abstract:

"Pharmacological glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and is an effective therapy for type 2 diabetes and obesity.

The use of GLP-1 medicines has revealed pleiotropic beneficial effects beyond glucose and weight control but little is known about the underlying basis of the pleiotropic effects.

Here, treatment of 20-month-old female C57BL/6 mice with the GLP-1R agonist semaglutide for 3 months improved physiological function, attenuated hallmarks of ageing and modulated nutrient sensors and conserved genetic regulators of ageing. Continued treatment extended mouse lifespan.

These effects parallel key features of calorie restriction, a dietary intervention that slows ageing, extends lifespan and alleviates a wide spectrum of ageing-associated diseases.

In a longitudinal study in direct comparison to matched calorie restriction, semaglutide treatment preserved baseline function and recapitulated many functional benefits of calorie restriction by attenuating age-associated decline, while also producing improvements above baseline and more favourable trajectories than calorie restriction in exploratory drive, spatial memory and glucose control.

Together, these findings demonstrate that GLP-1R activation initiated late in life slows ageing and extends lifespan in female mice, supporting its function as a calorie restriction mimetic and providing a mechanistic framework that may help to explain its broad beneficial effects while revealing effects beyond those attributable to reduced calorie intake."

Nature Briefing: Translational Research

Weight-loss drug slows ageing in female mice (behind paywall) "In one inbred strain of laboratory mice, late-life treatment with a GLP-1 drug extends lifespan. This effect might be more than just a consequence of calorie restriction."

Late-life semaglutide treatment slows ageing and extends lifespan in female mice (open access)

Fig. 1: GLP-1R activation late in life extends lifespan and improves physiological function.

Historic: Seniors Outnumber Young Kids Worldwide

Welcome to the Age of Gerontocracy! When will the young rebel? Demography is destiny!

"For the first time in recorded history, people 65 and older now outnumber children under 5 worldwide, according to a new U.S. Census report released this week. Falling birthrates and longer lives drove the milestone, which arrived earlier than demographers expected. ..."

Friday, September 4, 2026 - Join The Flyover

A study of more than 1,100 mammal and bird species found females outlast males in 72% of mammal species. Really!

Amazing stuff! However, this research is dated, published in October 2025!

" ... In birds, it’s the reverse."

"Females, whether they be human or some other type of mammal, like primates or even whales, tend to outlive men by an average of 5.4 years. ..."

"To the point

• Mammals vs birds: Among the 1,176 species studied, female mammals live on average 13 percent longer than males, while among birds, males live about five percent longer than females.
• Mating strategies play a role: In species with strong competition for mates – as is the case with most mammals – males die earlier. In monogamous species, such as many birds, males often live longer.
• Findings from zoos: Sex differences are more pronounced in wild populations than in zoos. This suggests that both genetic and environmental factors contribute to the discrepancy in life expectancy.

...

An international team ... conducted the most comprehensive analysis of sex differences in lifespan across mammals and birds to date.  ...

Across mammals, females usually live longer—for instance, in baboons and gorillas females often outlive males.

Yet this pattern is not universal: in many birds, insects, and reptiles, males are the longer-lived sex.

One genetic explanation, the heterogametic sex hypothesis, points to differences in sex chromosomes. In mammals, females have two X chromosomes, while males have only one X and one Y (making them the heterogametic sex). ...

Still, there was remarkable variation with many exceptions. “Some species showed the opposite of the expected pattern,” ... “For example, in many birds of prey, females are both larger and longer-lived than males. So sex chromosomes can only be part of the story.” ...

In addition to genetics, reproductive strategies also play a role. Through sexual selection, males in particular develop conspicuous characteristics such as colorful plumage, weapons, or large body size, which increase reproductive success but can shorten lifespan.

The new study supports this assumption: In polygamous mammals with strong competition, males generally die earlier than females.

Many birds, on the other hand, are monogamous, which means that competitive pressure is lower and males often live longer.

Overall, the differences were smallest in monogamous species, while polygamy and pronounced size differences were associated with a more pronounced advantage for females. ...

Parental care also plays a role. The researchers found evidence that the sex that invests more in raising offspring—in mammals, this is often the females—tends to live longer. In long-lived species such as primates, this is likely to be a selective advantage: females survive until their offspring are independent or sexually mature. 

Zoo life reduces—but does not erase—lifespan gaps

A long-standing idea is that environmental pressures—such as predation, pathogens, or harsh climates—drive the observed gaps between males and females. To test this, the researchers turned to zoo populations, where such pressures are largely absent. They found that lifespan gaps persisted even under these protected conditions.

Comparing zoo and wild populations showed that the gaps were often smaller in zoos but rarely disappeared—mirroring the human case, where advances in medicine and living conditions have narrowed but not eliminated the lifespan gap.

The findings suggest that sex differences in lifespan are deeply rooted in evolutionary processes—shaped by sexual selection and parental investment and that genetic differences in the sex determination system may also play a role. ..."

From the abstract:

"Across human cultures and historical periods, women, on average, live longer than men, a pattern best understood from a comparative evolutionary perspective. Here, we analyzed adult life expectancy in 528 mammal and 648 bird species in zoos. Like humans, 72% of mammals exhibited a female life expectancy advantage, while 68% of birds showed a male advantage, as expected from the harmful effects of sex chromosomes described by the heterogametic sex hypothesis.

Yet, sex differences varied widely. 

In zoos, we found strong evidence that this variation generally correlated with both the mating system and sexual size dimorphism.

Although with weaker evidence, the patterns remained consistent in populations from the wild, with an even larger effect of the mating system.

Thus, even in zoos, where environmental pressures are largely reduced, precopulatory sexual selection seems to play a fundamental role in shaping sex differences in life expectancy in mammals and birds."

Tuesday, September 1, 2026 - Join The Flyover

Why Do Women Live Longer Than Men?

Why women live longer than men - evolutionary insights on longevity (original news release, October 2025)

Sexual selection drives sex difference in adult life expectancy across mammals and birds (open access) "Study traces the evolutionary roots of the lifespan gap between women and men"

Globally, people are living longer, but spending more years in poor health

Food for thought! That sounds about right? This is a serious quality of life issue!

How much are individuals to be blamed e.g. for knowingly living significantly unhealthy lives?

What are the extra/additional healthcare costs associated with this?

"People around the world are living longer than ever before but spending more of those additional years in poor health, according to a new Global Burden of Disease (GBD) study published in The Lancet Public Health. ...

Researchers found that the global morbidity gap widened in almost all countries and territories analyzed between 1990 and 2023. Globally, while the share of life spent in poor health increased, trends varied by country, and a smaller number of countries saw this share decline.

Within a generation, the global morbidity gap widened by nearly two years, increasing from 8.8 years in 1990 to 10.7 years in 2023.

Globally, people spent an average of 14.5% of their lives in poor health in 2023, up from 13.6% in 1990.

Instead of occurring only in the final years of life, the widening morbidity gap was observed across the adult lifespan, suggesting that people are spending more years living with disease and disability throughout adulthood. ..."

From the abstract:

"Summary

Background

As survival improves globally, the central public health challenge increasingly shifts from extending life to extending healthy lifespan. The compression of morbidity hypothesis proposes that effective prevention and care will delay disability more than death, reducing the morbidity gap—ie, the duration or proportion of life spent in poor health.

We aimed to comprehensively estimate changes in the morbidity gap globally, regionally, and nationally from 1990 to 2023, by sociodemographic development levels and sex, and analysed leading diseases and injuries and their underlying risk factors contributing to years lived in poor health.

Methods

Using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates of life expectancy and healthy life expectancy (HALE) at birth for 204 countries and territories from 1990 to 2023, we calculated the morbidity gap as life expectancy minus HALE, and the proportional morbidity gap as this difference divided by life expectancy.

Results are presented globally, by GBD super-region and country, Socio-demographic Index (SDI) quintile, and sex.

We decomposed the morbidity gap into cause-specific and risk-specific contributions, assigning to each cause group its proportional share of years lived with disability (YLD), adjusted for comorbidity to avoid double counting disability for co-occurring conditions. We report mean estimates and 95% uncertainty intervals (UIs) derived from 250 or more draws from posterior distributions.

Findings

From 1990 to 2023, the global morbidity gap increased from 8·8 years (95% UI 6·7–11·2) to 10·7 (8·2–13·7), an increase of 1·9 years (1·3–2·6), or 21·9% (16·0–27·9), with point estimates suggesting widening morbidity gaps in 203 of 204 countries and territories.

Globally in 2023, an average of 14·5% of life was spent in poor health, compared to 13·6% in 1990. From 1990 to 2023, across locations, age-specific morbidity gaps widened across the adult life course, rather than concentrating in the final years of life.

In 2023, morbidity gaps were largest in the high SDI quintile and smallest in the low SDI quintile.

Countries with longer life expectancies had larger morbidity gaps and both had a positive relationship with SDI; however, the relationship between life expectancy and the proportional morbidity gap was less clear.

A small number of chronic, largely non-fatal causes were the primary contributors to the morbidity gap, with musculoskeletal disorders (especially low back pain), mental disorders (depressive and anxiety disorders), sense organ diseases (age-related hearing loss), unintentional injuries (falls), and other non-communicable diseases together accounting for 57·4% of unhealthy years in 2023, globally.

High fasting plasma glucose, high body-mass index, and child and maternal malnutrition were the leading risk factors contributing to the global morbidity gap.

Interpretation

The expansion of the morbidity gap across nearly all locations indicates that improvements in survival have consistently outpaced reductions in non-fatal health loss across geographies, SDI levels, and sexes, with most populations now spending a decade or more of life in poor health across the lifespan.

Progress towards healthy ageing should therefore be assessed not only by reduced mortality, but also by declines in years lived in poor health, with emphasis placed on extending healthspan. ..."

People are living longer, but spending more years in poor health

Global, regional, and national trends in the morbidity gap and contributing diseases, injuries, and risk factors, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023 (open access)

Figure 1 Morbidity gap by GBD super-region (A) and SDI quintile (B), 1990–2023

Figure 2 Comparison of the morbidity gap (A, B) and proportional morbidity gap (C, D) versus life expectancy across countries and territories, 1990 (A, C) and 2023 (B, D)

From Andhra Chilli To Rajasthani Thali: Is India's Love for Spice A Health Hack?

Recommendable! The hotter the food, the later the death!

(1549) From Andhra Chilli To Rajasthani Thali: Is India's Love for Spice A Health Hack? | Vantage | 4K - YouTube

Greenland deep-sea shark, the longest living vertebrate on the planet, can live for around 400 years

Amazing stuff!

"... But in April 2026, a group of researchers and volunteers stood on the cloudy shoreline of County Sligo, Ireland, and marvelled at the sight of a species that had never been stranded here before – a dead Greenland shark. 

Judging by its size – around 3m (10ft) long – the grey-beige animal lying on the tidal flats was over 150 years old. ... 

The Greenland shark, the longest living vertebrate on the planet, can live for around 400 years. ..."

"... The [recovered dead] shark is now undergoing detailed scientific postmortem examination, contributing valuable data to the understanding of this elusive deep-water species. Tissue samples and selected anatomical components are being preserved as part of the National Museum’s scientific collections, ensuring a permanent record of this exceptional specimen. ..."

'We were all just in awe': A stranding in Ireland sheds new light on the long, slow, ice-cold life of a deep-sea shark "Some Greenland sharks alive today may have been contemporaries of Shakespeare. With a scarred heart that beats for centuries and eyesight that doesn't fade, this deep-sea shark defies age-related decline."

Remains of a rare Greenland shark recovered (original news release) "The remains of a rare 3-metre-long Greenland shark (Somniosus microcephalus) has been successfully recovered from the shoreline in County Sligo, marking the first recorded stranding of this species on the Irish coast."

Source

Recovery of the remains of the dead shark

Universal molecular aging clock predicts death risk across multiple mammalian species

Amazing stuff!

"... A multinational team of researchers have now given us a powerful molecular clock that, with the help of biological markers, can predict age as well as the risk of death in mammals. ...

They discovered that certain genes serve as universal markers of aging, and that these genes behave almost identically across mammals as they get older, regardless of species. By analyzing gene expression of these markers across more than 11,000 samples from mice, rats, macaques, and humans, researchers developed a universal aging clock. ..."

"... The study also separated gene expression changes associated with aging and mortality into modules that represent different biological processes, such as inflammation, energy production, and extracellular matrix organization. The authors developed individual transcriptomic clocks for each module and showed that different diseases and medical or lifestyle interventions may affect biological age through distinct primary processes. ..."

From the abstract:

"Ageing and interventions modulate health and mortality, yet the underlying molecular mechanisms of this modulation remain unclear.

Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age and expected mortality, predicting lifespan-modulating interventions, time to death, chronic diseases and rejuvenation.

Ageing-related changes were conserved across species and cell types, revealing universal transcriptomic signatures of mammalian ageing and mortality, including CDKN1A and LGALS3, whose protein levels were also associated with mortality and multimorbidity in UK Biobank.

Mortality-associated features were recapitulated across in vivo and in vitro damage-accumulation models, including inflammation, replicative senescence, metabolic inhibition and γ-irradiation, and were attenuated or reversed by cell immortalization, reprogramming, heterochronic parabiosis and early embryogenesis.

Network analysis uncovered a modular architecture of ageing- and mortality-associated hallmarks, encompassing inflammation, interferon signalling, mitochondrial function, chromatin modification and extracellular matrix organization.

To quantify ageing of individual cellular components, we developed module-specific clocks, which revealed pathway-specific effects of interventions: chronic diseases primarily accelerated inflammatory-module ageing, whereas caloric restriction and Klotho (also known as Kl) deficiency targeted mitochondrial and metabolic modules.

Transcriptomic and DNA methylation clocks showed correlated age acceleration in human blood, which was strongest for the chromatin-associated module clock, highlighting mechanistic links between molecular ageing modalities. This study reveals conserved signatures and a modular architecture of mortality regulation, providing a framework for quantifying and targeting ageing of cellular subsystems across species and tissues."

Universal aging clock predicts death risk across multiple mammalian species

Gene Expression ‘Clocks’ Reveal Shared Molecular Signatures of Aging and Mortality Across Mammals (original news release) "Mass General Brigham researchers identify conserved gene expression signatures linked to biological aging and risk of disease and mortality, offering a new framework for quantifying aging and evaluating interventions that modulate healthspan and lifespan"

Gene-expression patterns can be used to estimate mortality risk and chronological age (no public access) "Massive analyses of RNA transcripts from rodents, monkeys and humans reveal hallmarks of ageing that could expedite the development of anti-ageing interventions."

Universal transcriptomic hallmarks of mammalian ageing and mortality (open access)

Fig. 1: Rodent multi-tissue transcriptomic clocks capture molecular changes associated with ageing and mortality.

Fig. 2: Transcriptomic biomarkers of ageing and mortality are conserved across mammalian species and cell types.

Clearing circular RNA from cells extends lifespan, C. elegans study reveals

Good news!

"... research team ... discovered the RNASEK protein—an enzyme that degrades circular RNA—plays a vital role in slowing aging and extending lifespan. The findings are published in the journal Molecular Cell. ...

they discovered the RNASEK protein—an enzyme that degrades circular RNA—plays a vital role in slowing aging and extending lifespan. ..."

From the highlights and abstract:

"Highlights

• RNK-1/RNASEK is a circRNA-cleaving ribonuclease that contributes to longevity

• The role of RNK-1 in aging and circRNA degradation is evolutionarily conserved

• RNK-1 regulates stress-granule dynamics by limiting age-associated circRNA levels

Summary

Circular RNAs (circRNAs) accumulate with age, but their functional impact on aging remains elusive. In this study, we reveal a mechanism by which ribonuclease κ (RNASEK) prevents age-dependent circRNA accumulation by promoting its degradation. Through a genetic screen targeting ribonucleases, we identified RNASEK as a specific circRNA-cleaving ribonuclease.

RNASEK is downregulated during aging, causing the age-dependent increase in circRNA levels. RNASEK is necessary and sufficient for lifespan extension and healthspan maintenance in Caenorhabditis elegans.

Mammalian RNASEK also directly degrades circRNAs and is required for preventing premature aging in cultured human cells and mice, indicating its evolutionarily conserved role.

Notably, we demonstrate that circRNAs localize within stress granules, where RNASEK, in collaboration with heat shock protein 90 (HSP90), prevents the toxic aggregation of circRNAs in aged organisms. Our study establishes RNASEK as a conserved regulator of aging and offers a strategy for targeting circRNAs to mitigate age-associated diseases and to extend organismal healthspan."

Clearing circular RNA from cells extends lifespan, C. elegans study reveals

Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules (no public access)

Graphical abstract

Your Death is Decided by Your Genes, Not Good Living with Molly Gambhir

Recommendable!

DNA variations explaining up to 50% of longevity differences

Amazing stuff! One reason why twin studies are so important!

"A new study points to a larger role for genetics than previous research had indicated, estimating the contribution of genes to determining human lifespan at about 50%. That is roughly double what prior research concluded, and it mirrors the findings of lifespan studies in laboratory animals. ..."

"... Surprisingly, for decades scientists believed that the heritability of human lifespan was relatively low compared to other human traits, standing at just 20 to 25 percent; some recent large-scale studies even placed it below 10 percent. ..."

From the editor's summary and abstract:

"Editor’s summary

... However, this is a difficult topic to study because it takes a long time to collect data on human life spans, and many different factors can contribute to mortality. One key distinction is between extrinsic mortality (violence, accidents, infections, etc.) and intrinsic mortality due to genetic mutations and/or aging-related diseases.

Shenhar et al. analyzed more than a century’s worth of data from three different Scandinavian twin cohorts and concluded that the current estimates of longevity heritability are much too low (see the Perspective by Bakula and Scheibye-Knudsen). In the late 1800s and early 1900s, when these study cohorts were born, extrinsic causes played a large role in mortality, but once those are excluded, longevity appears to be about 50% heritable, similar to many other traits. ...

Abstract

How heritable is human life span? If genetic heritability is high, longevity genes can reveal aging mechanisms and inform medicine and public health. However, current estimates of heritability are low—twin studies show heritability of only 20 to 25%, and recent large pedigree studies suggest it is as low as 6%.

Here we show that these estimates are confounded by extrinsic mortality—deaths caused by extrinsic factors such as accidents or infections. We use mathematical modeling and analyses of twin cohorts raised together and apart to correct for this factor, revealing that heritability of human life span due to intrinsic mortality is above 50%. Such high heritability is similar to that of most other complex human traits and to life-span heritability in other species."

Study finds greater role for genetics in driving human lifespan

Rethinking Longevity: Genes Matter More than We Thought (original news release) "Weizmann Institute study finds genetic contribution to human lifespan is about 50 percent – more than double previous estimates"

Rethinking the heritability of aging (open access) "The genetic contribution to human longevity is greater than previously thought"

Heritability of intrinsic human life span is about 50% when confounding factors are addressed (open access)

Credits: The Flyover

Fig. 1. Extrinsic mortality masks life-span correlations in twin cohorts.

Fig. 2. Life-span heritability increases when accounting for extrinsic mortality.

Eye-opening research: Greenland sharks maintain vision during their 4 centuries long life through DNA repair mechanism

Amazing stuff!

"... the longest-living vertebrate in the world  ... with opaque eyes that appear lifeless, except for the parasite latched to one of its eyeballs. Scientists have long suspected the large species to be functionally blind, given the frequent presence of the parasite and its exceptionally dim and obstructed visual environment.

Now, new research ... on Greenland shark vision ... is challenging what we know about aging, vision and longevity. ...

findings suggest that a DNA repair mechanism enables these sharks – some of which live for 400 years – to maintain their vision over centuries with no signs of retinal degeneration and that they are well adapted to extreme low-light conditions. ..."

From the abstract:

"The Greenland shark (Somniosus microcephalus) is the longest-living vertebrate and inhabits the exceptionally dim and cold waters of the Arctic deep sea. Due to its extreme lifespan, harsh environmental conditions, and prevalent corneal parasitisation, the Greenland shark has previously been thought to have impaired or degenerated vision.

Here, we present genomic, transcriptomic, histological and functional evidence that the Greenland shark retains an intact visual system well-adapted for life in dim light.

Histology and in vitro opsin expression revealed visual adaptations typical of deep-sea species, including densely packed, elongated rods and a short-wavelength shift in rod visual pigment sensitivity compared to shallow-water sharks. In situ hybridisation confirmed the presence of essential visual cell types: rods, Müller glia, and bipolar, amacrine, and ganglion cells.

Moreover, despite being over a century old, the examined specimens showed no obvious signs of retinal degeneration. Using whole genome and retinal RNA-sequencing, we further show that dim-light (rod-based) vision genes are intact and robustly expressed, while many bright-light (cone-based) vision genes have become pseudogenized and/or are no longer expressed.

Finally, we identify robust expression of DNA repair-associated genes in the retina, which may help support long-term maintenance of retinal integrity over the Greenland shark’s extreme lifespan."

Eye-opening research: Greenland sharks maintain vision for centuries through DNA repair mechanism

Eye-opening research (original news release) "... astonishing findings about Greenland sharks may lead to new ways of preserving vision as we age"

The visual system of the longest-living vertebrate, the Greenland shark (open access)

The deep sea Greenland shark

Fig. 1: Visual system of the Greenland shark.

Extracellular vesicles may hold a cure for cell aging

Good news! Closing in on the fountain of youth!

"... there’s a powerful new way to slow or even halt that deterioration, and it lies inside extracellular vesicles. Those are tiny, membranous particles, ranging from 10 microns down to 20 nanometers, that exit cells and dwell in the spaces among them.

In their ... paper “Embryonic stem cell-derived extracellular vesicles delay cellular senescence by inhibiting oxidative stress,” ... explore how extracellular vesicles from embryonic stem cells can protect other cells from oxidative stress. ..."

From the abstract:

"The accumulation of cells that permanently exit the cell cycle and undergo senescence is a hallmark of aging and predisposes organisms to disease.

Emerging evidence suggests extracellular vesicles (EVs) released by pluripotent embryonic stem cells (ESCs) possess therapeutic/regenerative properties with the potential to significantly impact cellular senescence and aging-related disorders. However, the critical next step for taking advantage of the potential benefits offered by ESC-derived EVs will be to unravel the molecular mechanisms responsible for their unique functional effects, which thus far have not been fully defined.

Toward that goal, we now identify a signaling pathway essential for EVs shed by ESCs to potently block fibroblasts and astrocytes from undergoing senescence.

It starts with the extracellular matrix protein fibronectin that coats the surfaces of EVs, enabling the vesicles to bind integrins on cells and trigger the activation of FAK and AKT. This leads to the inhibition of GSK3β activity and stabilization of the transcription factor Nrf2, which counteracts the effects of oxidative stress that would otherwise drive cellular senescence.

These findings define a signaling pathway used by ESC-derived EVs to extend cellular lifespan, highlighting their potential application in anti-aging strategies."

Extracellular vesicles may hold cure for cell aging

Embryonic stem cell-derived extracellular vesicles delay cellular senescence by inhibiting oxidative stress (open access)

Figure 8 Diagram showing how EVs produced by pluripotent ESCs delay cellular senescence. The MVs and exosomes produced by ESCs are coated with fibronectin, which can engage and activate integrins expressed in target cells. This results in the activation of a signaling pathway that inhibits GSK3β, increases the stability of Nrf2, and suppresses the accumulation of ROS that would otherwise trigger cells to undergo senescence.

Pre-Neolithic hunter-gatherer DNA may explain why some people live to 100 years or more

Amazing stuff! So it is not olive oil and mediterranean cuisine? Just kidding!

"... A new study ... found that Italian centenarians carry a higher proportion of genetic material from Western Hunter-Gatherers (WHG) compared to the general population. ..."

From the abstract:

"The genetics of human longevity has been primarily studied using classical methods developed in genome-wide association studies.

With the recent advances in paleogenomics, it is now possible to investigate to what extent ancient population ancestries contribute to complex traits.

In this study, we explored the role of ancient genetic components in human longevity by focusing on the Italian Peninsula, whose genetic heritage includes several past genetic ancestries that have contributed to the current European genetic make-up.

We analyzed genome-wide data of 333 Italian centenarians and 690 geographically matched healthy controls, and compared their genetic composition to 103 ancient genomes representative of the main past European population ancestries.

Our findings indicate that Italian centenarians have a higher genetic affinity with Western Hunter-Gatherer (WHG)-related ancestry compared to controls, according to PCA and f4-statistics.

Logistic regression models based on supervised admixture revealed a significant association between higher WHG ancestry and the centenarian status.

Additionally, residual-based predictive analysis showed that centenarians exhibit a significantly higher WHG contribution independent of the genetic structuring of the general Italian population.

By painting the chromosomes of modern Italians, we also showed a significantly higher number of WHG alleles at pro-longevity SNPs.

In the present study, we demonstrate the contribution of ancient genetic components to the longevity phenotype. In particular, we showed a greater contribution from Western Hunter-Gatherer-related ancestry to Italian centenarians, thus suggesting that this pre-Neolithic genetic component, which has been linked to population shifts occurring within Europe after the Last Glacial Maximum, could be beneficial for longevity today."

Ancient hunter-gatherer DNA may explain why some people live to 100 years or more

Western Hunter-Gatherer genetic ancestry contributes to human longevity in the Italian population (open access)

Fig. 2 Results of the PCA projection analysis.
A Scatterplot with genetic components of 333 CENT, 690 ITA, and selected ancient individuals from the four basal ancient ancestral groups (47 WHG, 14 Iran_N/CHG, 26 Turkey_N, and 16 Yamnaya_EBA) projected onto the modern Euro-Mediterranean reference space.
B Boxplots displaying the distribution of Euclidean distances between CENT or ITA individuals and the centroid of each of the four considered ancestral groups

The multiomics blueprint of the individual with the most extreme lifespan (died at age 117)

Amazing stuff! Scientists studied the genes of a woman (Maria Branyas Morera from Spain) who lived 117 years.

From the highlights and abstract:

"Highlights

• (Epi)genome, transcriptome, metabolome, proteome, and microbiome study of the oldest human

• Despite molecular hallmarks of aging, absence of major age-associated diseases

• Resilient genetic variants and low-inflammation metabolic profile reduce aging risks

• Bacteria occurrence and epigenome profile resembling younger individuals

Summary

Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world’s oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts.

The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions."

The multiomics blueprint of the individual with the most extreme lifespan - ScienceDirect

Maria Branyas Morera on her 117th birthday (Source)

Graphical abstract

Did Chinese Scientists Just Find The Answer To Anti-Ageing in mole rats? with Molly Gambhir

Very recommendable!

Drug aims to block cell death to fight aging

Methuselah is smiling!

A LinkGevity motto "Pioneering Anti-Necrotics™"

"A UK start-up has designed a drug to slow aging by preventing necrosis — early cell death in response to injury or illness. LinkGevity says that its drug Link-001 has prevented necrosis in lab-grown models of human organs, by stopping the flow of calcium ions into cells. The company plans to test its anti-necrosis drug in people with damaged kidneys later this year, if it can win regulatory approval. Link-001 is a combination of two already-approved drugs, which LinkGevity hopes will help it move into the clinic quickly. To date, no longevity drugs have been approved because of debate over the underlying mechanisms of aging and relevant biomarkers."

Nature Briefing: Translational Research

Start-up takes aim at ageing with drug to block cell death (behind paywall)

But the company's pipelines are kept very vague. Secrecy or?

The beautiful mind behind this longevity research: Dr. Carina Kern, CEO of LinkGevity

Amino acid Betaine can reproduce some of the benefits of exercise and slow some signs of ageing

Good news (for older, exercising males)!

"Exercise benefits — without the workout

When fed to mice, betaine — a modified amino acid made by the kidneys and involved in metabolism — can reproduce some of the benefits of exercise and slow some signs of ageing. Researchers found that old mice given water spiked with the molecule had stronger muscles, less inflammation and more youthful skin than their counterparts who did not get the supplement. Whether it would have the same effect in humans is unclear, but even if it did, it couldn’t replicate all of the myriad benefits of exercise ..."

From the highlights and abstract:

"Highlights

• Systematic molecular blueprint of how exercise reshapes human homeostasis

• Repeated exercise boosts circulating betaine partly via renal synthesis

• Betaine inhibits TBK1, reducing senescence and inflammation

• Betaine exerts multi-organ geroprotection in aged mice

Summary

Exercise has well-established health benefits, yet its molecular underpinnings remain incompletely understood. We conducted an integrated multi-omics analysis to compare the effects of acute vs. long-term exercise in healthy males. 

Acute exercise induced transient responses, whereas repeated exercise triggered adaptive changes, notably reducing cellular senescence and inflammation and enhancing betaine metabolism.

Exercise-driven betaine enrichment, partly mediated by renal biosynthesis, exerts geroprotective effects and rescues age-related health decline in mice.

Betaine binds to and inhibits TANK-binding kinase 1 (TBK1), retarding the kinetics of aging. These findings systematically elucidate the molecular benefits of exercise and position betaine as an exercise mimetic for healthy aging."

Nature Briefing: Translational Research

Can a pill replace exercise? Swigging this molecule gives mice benefits of working out (behind paywall) "Betaine, a compound that becomes more abundant in men who take up jogging, could confer some of the anti-ageing advantages of physical activity."

Systematic profiling reveals betaine as an exercise mimetic for geroprotection (no public access)

Graphical abstract

FGF21 is a hormone having a variety of beneficial metabolic effects in older mice

Good news! In the future, maybe more hormones, less vitamins & minerals?

"Fibroblast growth factor 21 (FGF21) is a hormone that is primarily produced in the liver, as well as in adipocytes and some other tissues. It has been reported to have a variety of beneficial metabolic effects, but there has been no clear mechanistic explanation for them.

Using mouse models of adipocyte-specific overexpression of FGF21, Gliniak et al. demonstrated that these animals are protected from obesity and live longer overall without losing lean tissue mass or bone mineral density. These beneficial effects of FGF21 were due to a variety of effects on different tissues and organs, including increased energy expenditure, improved insulin sensitivity, and decreased adipose tissue ceramide buildup and inflammation, all of which help to explain the health benefits attributed to this hormone."

From the highlights and abstract:

"Highlights

• FGF21 overexpression in the adult mouse increases survival that is not linked to trade-offs in organismal growth

• FGF21 overexpression prevents obesity, liver steatosis, and loss of lean mass in gerobese mice fed a HFD

• Elevated FGF21 increases energy expenditure but does not affect cold tolerance in mice fed a HFD

• FGF21 reduces ceramide levels in visceral adipose tissue by adiponectin-independent mechanisms

Summary

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues.

Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan.

To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis.

Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence of adiponectin, a hormone known to regulate ceramide breakdown.

These results suggest that fat tissue is a central site for FGF21’s beneficial effects and point to its potential for treating metabolic syndrome and age-related diseases by promoting a healthier metabolic profile under dietary stress and extending healthspan and lifespan."

In Other Journals | Science

FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression (open access)

Graphical abstract