Biology subjects

Stern, N.

Publications and source records attributed to Stern, N..

7 recordsLinked to original sources

bioRxiv2026

The Metabolic Scope Theory of Aging: Rising Mitochondrial Impedance Compresses Metabolic Reserve to Constrain Lifespan

Maximum lifespan varies more than 100-fold across vertebrates, yet within each species aging emerges as a coordinated syndrome spanning metabolism, immunity, endocrine signaling, cognition, and regeneration. We propose the Metabolic Scope Theory of Aging (MSTA), which treats longevity as the time required to exhaust mitochondrial bioenergetic reserve rather than as a consequence of resting metabolic rate alone. The framework decomposes lifespan into three physical axes: Scope, the reserve capacity that buffers cumulative damage; Stability, the resistance of mtDNA-linked OXPHOS architecture to erosion; and Pace, the temperature-dependent kinetics of lesion accumulation. Using body mass as a Scope proxy, mtDNA GC content as a Stability proxy, and body temperature as Pace, the resulting Scope-Stability-Pace relation, lnMLS = lnBM + {beta} GC% -{gamma} Tb + c, explains [~]69% of mammalian maximum-lifespan variance across 379 species. Cross-class comparisons reinforce the same constraint structure: birds offset high thermal Pace through elevated mtDNA Stability, and the SSP temperature coefficient derived from mammals matches the temperature dependence of lifespan observed in ectotherms. The framework further connects comparative lifespan scaling to Gompertz-like mortality acceleration through progressive reserve erosion and threshold crossing. Mechanistically, MSTA models cumulative mtDNA-linked damage as rising impedance within OXPHOS. Increasing internal resistance drives mitochondria toward a high-redox-pressure, low-current regime that preserves basal ATP while restricting NAD+ regeneration, CoQ acceptor availability, and {Delta}p-dependent work. The earliest failure is therefore not energetic collapse but loss of regenerative scope: NAD+-gated TCA flux, aspartate and nucleotide synthesis, one-carbon metabolism, and redox-buffered repair become progressively harder to sustain, and diverse age- related pathologies emerge as tissue-specific projections of this shared upstream constraint. MSTA separates a reversible, operational impedance (redox poise, membrane potential, endocrine tone) from a fixed, informational one (accumulated mtDNA damage) that sets the hard ceiling on lifespan. Because the informational layer cannot be reversed by regulatory means, the framework predicts that until therapies can directly restore mitochondrial conductance, interventions will be most effective when they relieve redox pressure or bypass constrained biosynthetic gates.

physiology↗

bioRxiv2025

Improving retention time of Indocyanine Green for in vivo two-photon microscopy using liposomal encapsulation

We propose a technique for improving the retention time of Indocyanine Green (ICG), an FDA-approved, widely available, near infrared (NIR) probe for in vivo imaging of the cerebrovascular structure in rodents. We present a synthesis process for liposomal nanoparticles that, when used to encapsulate ICG, significantly increase the circulation time of the vascular label. Further, we conduct in vivo imaging experiments with unencapsuated (free) ICG and liposomal ICG (L-ICG) and compare the retention of ICG in the vascular network. Our work tackles one of the most fundamental limitations in using ICG i.e. rapid clearance, for the purpose of two-photon microscopy.

neuroscience↗

bioRxiv2024

Proposed network of Marine Protected Areas supports larval dispersal and connectivity in the Eastern Mediterranean

The marine environment of the Eastern Mediterranean is under growing threat due to natural and anthropogenic stressors. Networks of Marine Protected Areas (MPAs) are effective tools in protecting marine environments and conserving their biodiversity. Currently, only 4% of the Israeli territorial waters are declared as MPAs, however six new MPAs, which will encompass more than 20% of the Israeli territorial waters, are planned. A central component in the effectiveness of MPAs is the degree to which the protected populations are connected. The purpose of our study is performing a comprehensive connectivity analysis for the proposed network of MPAs. We find that the proposed network substantially supports local and regional larval connectivity patterns for five target species in terms of the number of recruits, betweenness centrality, as well as the number of regional and local MPAs connections. Overall, the results provide strong support for the efficiency of the proposed MPAs in facilitating local and regional larval connectivity. Our findings will be useful for marine spatial planning and natural resource management and will enhance the protection and conservation of our marine environment.

ecology↗

bioRxiv2022

Epigenetic aging waves:Artificial intelligence detects clustering of switch points in DNA methylation rate in defined sex-dependent age periods

BackgroundAging is linked to hypermethylation of CpG sites on promoters and enhancers, along with loss of methylation in intergenic zones. That such changes are not necessarily a continuous process is exemplified by the extensive changes in DNA methylation during development with another significant time of change during adolescence. However, the relation between age and DNA methylation during adult life has not been systematically evaluated. In particular, potential changes in methylation trends in the same CpGs over the years that may occur with aging remain largely unexplored. MethodsHere we set out to determine the average trends by age of the CpG sites represented in the Illumina 450 platform, based on data from 2143 subjects of the age range of 20 to 80 years, compiled from 24 different cohorts. Using several mathematical procedures, we initially separated stationary probes from probes whose methylation changes with age. Among the latter, representing [~]20% of the probes, we then focused on the identification of CpG sites with switch points, i.e., a point where a stable trend of change in the age-averaged methylation is replaced by another linear trend. ResultsUsing several mathematical modeling steps, we generated a machine learning model that identified 5175 CpG sites with switch points in age-related changes in the trend of methylation over the years. Switch points reflect acceleration, deceleration or change of direction of the alteration of methylation with age. The 5175 switch points were limited to 2813 genes in three waves, 80% of which were identical in men and women. A medium-size wave was seen in the early forties, succeeded by a dominant wave as of the late fifties, lasting up to 8 years each. Waves appeared[~]4-5 years earlier in men. No switch points were detected on CpGs mapped to the X chromosome. ConclusionIn non-stationary CpG sites, concomitant switch points in age related changes in methylations can be seen in a defined group of sites and genes, which cluster in 3 age- and sex-specific waves.

genomics↗

bioRxiv2022

Trophic ecology of deep-sea megafauna in the ultra-oligotrophic Southeastern Mediterranean Sea

The trophic ecology of fourteen species of bathybenthic and bathypelagic fishes and six species of bathybenthic decapod crustaceans from the continental slope and rise of the Southeastern Mediterranean Sea (SEMS) was examined using stable isotope analysis. Mean {delta}13C values among fish species varied by more than 4.0{per thousand}, from -20.85{per thousand} (Macroramphosus scolopax) to -16.57{per thousand} (Conger conger and Centrophorus granulosus), and increased as a function of depth (200 - 1400 m). Mean {delta}13C values of the crustaceans showed smaller variation, between -16.38{per thousand} (Polycheles typhlops) and -18.50{per thousand} (Aristeus antennatus). This suggests a shift from pelagic to regenerated benthic carbon sources with depth. Benthic carbon regeneration is further supported by the low benthic-pelagic POM-{delta}13C values, averaging -24.7 {+/-} 1.2{per thousand}, and the mixing model results, presenting very low contribution of epipelagic POM to the bathyal fauna. Mean {delta}15N values of fish and crustacean species ranged 7.91 {+/-} 0.36{per thousand} to 11.36 {+/-} 0.39{per thousand} and 6.15 {+/-} 0.31{per thousand} to 7.69 {+/-} 0.37{per thousand}, respectively, resulting in trophic position estimates, occupying the third and the fourth trophic levels. Thus, despite the proximity to the more productive areas of the shallow shelf, low number of trophic levels (TL~1.0) and narrow isotopic niche breadths (SEAc <1) were observed for bathybenthic crustaceans (TL = 3.62 {+/-} 0.22) and bathypelagic fishes (TL = 4.33 {+/-} 0.34) in the study area - probably due to the ultra-oligotrophic state of the SEMS resulting in limited carbon sources. Our results, which provide the first trophic description of deep-sea megafauna in the SEMS, offer insight into the carbon sources and food web structure of deep-sea ecosystems in oligotrophic marginal seas, and can be further used in ecological modeling and support the sustainable management of marine resources in the deep Levantine Sea.

ecology↗

bioRxiv2021

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns

BackgroundThe epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging. ResultsUsing the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the interpersonal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age. ConclusionsOf the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.

developmental biology↗

bioRxiv2019

PROMO: An interactive tool for analyzing clinically-labeled multi-omic cancer datasets

BackgroundAnalysis of large genomic datasets along with their accompanying clinical information has shown great promise in cancer research over the last decade. Such datasets typically include thousands of samples, each measured by one or several high-throughput technologies ( omics) and annotated with extensive clinical information. While instrumental for fulfilling the promise of personalized medicine, the analysis and visualization of such large datasets is challenging and necessitates programming skills and familiarity with a large array of software tools to be used for the various steps of the analysis.\n\nResultsWe developed PROMO (Profiler of Multi-Omic data), a friendly, fully interactive stand-alone software for analyzing large genomic cancer datasets together with their associated clinical information. The tool provides an array of built-in methods and algorithms for importing, preprocessing, visualizing, clustering, clinical label enrichment testing and survival analysis that can be performed on a single or multi-omic dataset. The tool can be used for quick exploration and for stratification of tumor samples taken from patients into clinically significant molecular subtypes. Identification of prognostic biomarkers and generation of simple subtype classifiers are additional important features. We review PROMOs main features and demonstrate its analysis capabilities on a breast cancer cohort from TCGA.\n\nConclusionsPROMO provides a single integrated solution for swiftly performing a complete analysis of cancer genomic data for subtype discovery and biomarker identification without writing a single line of code, and can, therefore, make the analysis of these data much easier for cancer biologists and biomedical researchers. PROMO is freely available for download at http://acgt.cs.tau.ac.il/promo/.

bioinformatics↗