Insulin signalling extends lifespan across species but, in Drosophila, this effect can vary among populations. This variable response is underpinned by epistasis between mtDNA and nDNA.
Category: life extension – Page 6
Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis
In healthy aging strategies, nutritional supplements synergize with optimized dietary and lifestyle interventions by modulating aging-related molecular pathways.[ 8, 9 ] Notably, NMN exerts multi-organ anti-aging effects by elevating NAD+ levels to activate the SIRT1 pathway, thereby significantly enhancing mitochondrial function while reducing oxidative stress and DNA damage.[ 10 ] Similarly, curcumin delays aging and related diseases through pleiotropic mechanisms involving oxidative stress regulation, anti-inflammatory actions, telomere maintenance, and sirtuin protein modulation.[ 11 ] However, practical applications face significant challenges: bioactive compounds like resveratrol and curcumin suffer from limited bioavailability due to poor aqueous solubility and first-pass metabolism, while excessive supplementation of antioxidants such as vitamins C/E may disrupt reactive oxygen species (ROS) signaling homeostasis, potentially inducing cellular toxicity or even increasing hemorrhagic risk.[ 12-14 ] Future development of anti-aging supplements should focus on: 1) innovative formulation strategies to enhance bioavailability; 2) optimized dosing regimens to minimize toxicity; and 3) long-term clinical studies to validate efficacy.
Selenium, an essential trace element with diverse biological activities, plays a critical role in healthy aging.[ 15-17 ] ≈1 billion people worldwide are affected by selenium deficiency, which is closely linked to neurological disorders, cardiovascular abnormalities, malignancies, and immune dysfunction.[ 18-20 ] Substantial evidence supports the anti-aging effects of selenium through multiple mechanisms: 1) Selenomethionine (SeMet) effectively suppresses Fe2+/H2O2- or Aβ-induced free radical generation, demonstrating therapeutic potential for Alzheimer’s disease characterized by oxidative stress;[ 21 ] 2) Selenium supplementation elevates serum GPx3 levels, a selenoprotein predominantly localized in the basement membrane of renal proximal tubules, modulating mitochondrial quality control pathways to mitigate heavy metal-induced renal aging;[ 22 ] and 3) Our recent findings reveal that selenium supplementation significantly attenuates age-related muscle atrophy by preserving redox homeostasis and regulating muscle protein metabolism.[ 23 ] Recent clinical trials in patients with advanced non-small cell lung cancer (NSCLC) demonstrated that oral administration of selenium nanoparticles (SeNPs) as a dietary supplement (200 µg day−1) in combination with Bev+AP chemotherapy significantly enhanced therapeutic outcomes compared to chemotherapy alone. The SeNPs combination group showed remarkable tumor regression, with progression disease rates decreasing dramatically from 50% to 0% and partial response rates increasing to 83.3%, along with significantly improved objective response rate and disease control rate.[ 24 ] Importantly, this regimen maintained excellent safety profiles without triggering fluctuations in pro-inflammatory or immunosuppressive cytokines. These compelling findings not only establish SeNPs as a safe and effective adjuvant therapy for advanced NSCLC but also provide valuable clinical translation data for nano-selenium formulations in oncology. Despite selenium’s proven benefits in reducing oxidative damage, maintaining genomic stability, and delaying telomere shortening, its narrow therapeutic window, limited bioavailability, and specific mechanisms in multi-organ protection during natural aging require further investigation.
Nanodelivery carriers have emerged as a next-generation platform for gene and drug delivery, offering tunable physicochemical properties such as size, composition, and surface modifications.[ 25 ] Our team has developed organically-bridged mesoporous silica nanoparticles (MSNs) by incorporating functional diselenide bonds into the silica framework at the molecular level, addressing the critical challenge of poor biodegradability in conventional silica materials.[ 26 ] This nanocarrier exhibits unique dual redox-responsive properties, allowing for more precise maintenance of redox homeostasis compared to traditional antioxidants, aligning with the core goal of preserving organismal homeostasis in anti-aging research. Building on this breakthrough, a comprehensive research framework was established: first, this study constructed a natural aging mouse model with MSNs, disulfide-bridged MSNs (SMSNs), commercially available SeMet as controls and then compared the effects of diselenide-bridged MSNs (SeMSNs) on lifespan extension, frailty delay, and multi-organ anti-aging. Next, key pathways and targets were identified through multi-organ transcriptome sequencing, followed by in-depth mechanistic studies. Finally, clinical translation was integrated by analyzing the correlation between serum selenium levels and aging biomarkers in the elderly, and validating the clinical effects of SeMSNs using primary adipose precursor cells (APCs) models. This systematic approach provides a solid theoretical foundation and clinical evidence for the application of nano-selenium in anti-aging research.
The Wnt–NAD+ axis in cancer, aging, and tissue regeneration
Wnt–NAD+ axis in stem cell function.
The Wnt–NAD+ axis is a fundamental regulatory hub in which metabolic state meets developmental signaling and it acts as a metabolic sensor that coordinates tissue regeneration with cellular energy status through compartment specific NAD+ pools.
Wnt signaling regulates NAD+ metabolism by controlling the expression of key biosynthetic enzymes and NAD+ consumers, while NAD+-dependent proteins modulate Wnt activity through direct interactions and epigenetic modifications.
Sirtuins exhibit tissue-specific and subcellular compartment-dependent roles in Wnt regulation where they function as activators or suppressors depending on the cellular bioenergetic state.
The Wnt–NAD+ axis maintains stem cell function and self-renewal capacity through metabolic/signaling integration, and its disruption during aging leads to declining regenerative capacity.
The progressive dysregulation of compartment-specific Wnt–NAD+ coordination contributes to stem cell exhaustion and multiple pathological conditions, indicating that therapeutic strategies must consider tissue-specific and subcellular targeting. sciencenewshighlights ScienceMission https://sciencemission.com/Wnt%E2%80%93NAD-axis
Episode 2 — The Prospect of Immortality & Human Cryopreservation
Host: Kyle O’Brien — https://twitter.com/analog_kyle.
Guest: Emil Kendziorra — https://twitter.com/emilkendziorra.
Founder of @TomorrowBio.
Theme || the prospect of immortality & human cryopreservation.
Is Death just a Technical Problem we haven’t solved yet?
In this episode of State Change, Kyle O’Brien sits down with Emil Kendziorra, founder of Tomorrow Bio, to explore the science, ethics, and future of cryopreservation — the process that may one day allow humans (and even pets) to be revived centuries from now.
We talk about the brain, identity, consciousness, why people fear death, and what it means to rewrite the social contract when life extension becomes real.
Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification
Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.
The authors have declared no competing interest.
Scientists Identify Key Protein That Could Reverse Brain Aging
The study findings also suggest approaches that enhance expression or activity of DMTF1 may have therapeutic potential in reversing or delaying aging-associated decline of neural stem cell function.
While the preliminary findings stemmed mainly from in vitro experiments, the researchers hope to explore if elevating DMTF1 expression can regenerate neural stem cell numbers as well as improve learning and memory under the conditions of telomere shortening and natural aging, without increasing the risk of brain tumors. The long-term objective is to discover small molecules that can enhance DMTF1 expression and activity to improve the function of aged neural stem cells.
“Our findings suggest that DMTF1 can contribute to neural stem cell multiplication in neurological aging,” Dr Liang said. “While our study is in its infancy, the findings provide a framework for understanding how aging-associated molecular changes affect neural stem cell behavior, and may ultimately guide the development of successful therapeutics.”