This Perspective highlights the failures of an ageing cell in properly maintaining mRNA health at the various steps of the mRNA life cycle that result in vulnerability to disease, pointing to RNA imbalance as an emerging hallmark of cellular ageing.
Category: life extension
Why Some People Have Endless Energy (And Others Never Will)
From the article:
To put this in quantitative terms: consider an individual at the 5th percentile of genetic vitality. Even with an impeccable lifestyle, such a person might only reach the 25th percentile of vitality (energy levels, mood, motivation). Now consider someone at the 95th percentile of genetic vitality. Even with a mediocre or actively harmful lifestyle, this person might still operate at the 75th percentile or above. The gap between these two individuals, after both have optimized (or neglected) every modifiable factor, is entirely genetic.
The single most effective thing one can do to guarantee great energy, mood, motivation, metabolism, cognition, physique, and longevity is to pick the right parents.
This is not to say that lifestyle, hormones, and pharmaceuticals are unimportant. They clearly matter, often enormously. Rather, the point is that these interventions operate within a window whose size, position, and ceiling are defined by inherited genetic variation.
Vitality is affected by many things which I extensively discuss on my blog. These include metabolic health, hormones, inflammation, diet, exercise, and sleep, among other things. Each of these domains is important, and each is modifiable to varying degrees through lifestyle choices, pharmaceutical interventions, or behavioral change.
However, every one of these discussions has implicitly assumed a background variable that I have largely unaddressed: genetics.
Blood Test #2 In 2026: Biological Age, CVD Risk, Correlations With Diet
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Discount Links/Affiliates:
Blood testing (where I get the majority of my labs, for those who blood test with Quest): https://www.ultalabtests.com/partners… those who blood test with LabCorp: https://www.anrdoezrs.net/click-10161… At-Home Metabolomics: https://www.iollo.com?ref=michael-lus… Use Code: CONQUERAGING At Checkout Clearly Filtered Water Filter: https://get.aspr.app/SHoPY Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=… Use Code: CONQUERAGING NAD+ Quantification: https://www.jinfiniti.com/intracellul… Use Code: ConquerAging At Checkout Oral Microbiome: https://www.bristlehealth.com/?ref=mi… Enter Code: ConquerAging SiphoxHealth Blood Testing (ApoB, GrimAge): https://siphoxhealth.com/mlustgarten Green Tea: https://www.ochaandco.com/?ref=fqbtflod Use Code: ML10OFF Diet Tracking: https://shareasale.com/r.cfm?b=139013… If you’d like to support the channel, you can do that with the website, Buy Me A Coffee: https://www.buymeacoffee.com/mlhnrca Conquer Aging Or Die Trying Merch! https://my-store-d4e7df.creator-sprin…
Blood Testing Essentials (Biological Age, CVD-Risk, Kidney Health and Function):
PhenoAge (Biological Age): https://www.ultalabtests.com/partners…
Risk-weighted ApoB (a better CVD predictor than LDL, non-HDL cholesterol, and ApoB): https://www.ultalabtests.com/partners…
Kidney health and function: https://www.ultalabtests.com/partners…
Human Mind in a Theistic World
What happens to the human mind if God exists? Louis Caruana argues that mind, soul, and body are not separate entities but dimensions of a single human individual — challenging both strong dualism and reductive materialism while reframing what could survive death.
0:00 Human Mind in a Theistic World.
1:22 Mind, Soul, and the Individual.
4:33 Theism and Human Dignity.
5:17 Why Death Remains Tragic.
6:36 Resurrection and the Immortal Soul.
Louis Caruana SJ is a Jesuit priest ordained in 1991 and holds degrees in science, philosophy, and theology. He obtained his PhD from the University of Cambridge, and is now Dean of Philosophy at the Gregorian University, Rome, and Research Associate of Heythrop College, University of London.
More from Louis Caruana on Closer To Truth:
https://closertotruth.com/contributor…
Fisetin Attenuates D-Gal-Induced Ovarian Aging by Modulating Mitophagy via the AMPK/mTOR Pathway
This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers.
Decoding intended speech with an intracortical brain-computer interface in a person with long-standing anarthria and locked-in syndrome
This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers. Furthermore, fisetin reduced the number of atretic follicles and the extent of ovarian fibrosis and senescence, while simultaneously restoring the proliferation-apoptosis balance in follicular GCs, as well as alleviating oxidative stress. RNA-sequencing revealed that AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling and mitophagy were involved in the protective effects of fisetin against ovarian aging. Consistently, fisetin treatment promoted mitophagy, accompanied by AMPK/mTOR activation in ovarian tissues and GCs following D-gal exposure. Inhibition of AMPK attenuated the effect of fisetin on mitophagy. Additionally, blockage of mitophagy also reversed the beneficial effects of fisetin on mitochondrial injury, oxidative stress, cell cycle arrest, and cellular senescence in D-gal-induced senescent GCs. These findings indicate that fisetin prevents ovarian aging by suppressing follicular GC oxidative damage and ameliorating cell cycle arrest via activation of AMPK/mTOR-mediated mitophagy, thereby preserving female fertility.
Sleep Duration Linked to Accelerated Aging
The relationship between sleep and disease suggests that there exists a connection between the brain and the body that extends beyond merely influencing the brain itself.
Among brain-related disorders, short sleep was significantly associated with depressive episodes and anxiety disorders, as seen in other studies of sleep and mental health. Short sleep was also associated with obesity, type 2 diabetes, hypertension, ischemic heart disease, and heart arrhythmias.
Short and long sleep were associated with chronic obstructive pulmonary disease, asthma, and a cluster of digestive disorders, including gastritis and gastroesophageal reflux disease.
Cancer. Aging. Coma
A new longevity platform is showing promise across multiple diseases including potential applications in neurologic trauma and coma states. Researchers say the same underlying science could reshape how we think about aging itself.
Enhancing Non-small Cell Lung Cancer Susceptibility to Anti-PD-1/PD-L1 Therapy through PD-L1 Ligand–Ir(III) Complex Conjugates
Immunotherapy targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) has transformed the management of several types of cancers, including non-oncogene-addicted non-small cell lung cancer (NSCLC) [1], although its efficacy remains limited by resistance mechanisms and constraints inherent to monoclonal antibodies [1]. To overcome these drawbacks, small-molecule PD-L1 inhibitors have been developed, and we previously contributed by identifying the nanomolar triazine-based ligand Tr-10 [2]. In parallel, combinatorial strategies aimed at improving the efficacy of anti-PD-1/PD-L1 immunotherapy have gained increasing attention. Notably, platinum-based chemotherapy combined with immune checkpoint inhibitors is recommended as a first-line treatment for advanced NSCLC with PD-L1 expression <50% [3]. Here, we investigated a novel combination involving our anti-PD-L1, Tr-10 [2], and a bis(phenyl-pyridine)iridium(III) complex, Ir-2 (Fig. 1A) [4]. Iridium (Ir) complexes, unlike platinum drugs, are chemically inert and induce endoplasmic reticulum (ER) stress and overproduction of reactive oxygen species (ROS) [5,6], both culminating in damage-associated molecular pattern (DAMP) release and immunogenic cell death (ICD). Moreover, their photophysical properties enable PD-L1-targeted bioimaging when coupled with PD-L1 ligands (Fig. S1) [7].