The evolution of aging and lifespan

Trends in Genetics, Journal Year: 2023, Volume and Issue: 39(11), P. 830 - 843

Published: Sept. 14, 2023

Aging is a nearly inescapable trait among organisms yet lifespan varies tremendously across different species and spans several orders of magnitude in vertebrates alone. This vast phenotypic diversity driven by distinct evolutionary trajectories tradeoffs that are reflected patterns diversification constraint organismal genomes. Age-specific impacts selection also shape allele frequencies populations, thus impacting disease susceptibility environment-specific mortality risk. Further, the mutational processes spawn this genetic both germline somatic cells strongly influenced age life history. We discuss recent advances our understanding evolution aging at organismal, population, cellular scales, highlight outstanding questions remain unanswered.

Language: Английский

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DNA repair and anti-cancer mechanisms in the longest-living mammal: the bowhead whale

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 8, 2023

Abstract At over 200 years, the maximum lifespan of bowhead whale exceeds that all other mammals. The is also second-largest animal on Earth, reaching 80,000 kg 1 . Despite its very large number cells and long lifespan, not highly cancer-prone, an incongruity termed Peto’s Paradox 2 This phenomenon has been explained by evolution additional tumor suppressor genes in larger animals, supported research elephants demonstrating expansion p53 gene 3–5 Here we show fibroblasts undergo oncogenic transformation after disruption fewer suppressors than required for human fibroblasts. However, analysis DNA repair revealed double strand breaks (DSBs) mismatches with uniquely high efficiency accuracy compared to protein CIRBP, implicated protection from genotoxic stress, was present abundance relative We CIRBP downstream RPA2, at levels cells, increase fidelity cells. These results indicate rather possessing as barriers oncogenesis, relies more accurate efficient preserve genome integrity. strategy which does eliminate damaged but repairs them may be critical cancer-free whale.

Language: Английский

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Regulation of eukaryotic transcription initiation in response to cellular stress

Gene, Journal Year: 2024, Volume and Issue: 924, P. 148616 - 148616

Published: May 23, 2024

Language: Английский

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A Reexamination of Peto’s Paradox: Insights Gained from Human Adaptation to Varied Levels of Ionizing and Non-ionizing Radiation

Journal of Biomedical Physics and Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Humans have generally evolved some adaptations to protect against UV and different levels of background ionizing radiation. Similarly, elephants whales cancer, such as multiple copies the tumor suppressor gene p53, due their large size long lifespan. The difference in cancer protection strategies between humans elephants/whales depends on genetics, lifestyle, environmental exposures, evolutionary pressures. In this paper, present how differences could explain why a protective mechanism whereas not. living regions with high radiation, e.g. Ramsar, Iran where exposure rates exceed those surface Mars, seem developed kind However, general not cancer-fighting adaptations, so they instead rely medical technologies interventions. we discuss Studying elephant may provide insights into new prevention treatment for humans, but further research is required fully understand disparities.

Language: Английский

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Thermal stress, p53 structures and learning from elephants

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 7, 2024

As species adapt to climatic changes, temperature-dependent functions of p53 in development, metabolism and cancer will as well. Structural analyses epitopes interacting response environmental stressors, such heat, may uncover physiologically relevant cell regulation genomic adaptations. Here we explore the multiple elephant paradigm with an experimentally validated silico model showing that under heat stress some copies escape negative by MDM2 E3 ubiquitin ligase. Multiple isoforms have evolved naturally thus presenting a unique experimental system study scope contribution stressors DNA damage. We assert fundamental insights derived from studies historically heat-challenged mammal provide important directly human biology light climate change when 'heat' introduce novel challenges our bodies health.

Language: Английский

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Engineering Asian elephant TP53: TP53 retrogene knockouts activate common and unique cancer-relevant pathways

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Abstract TP53 functions as a central regulator in response to DNA damage and other cell stressors by inducing the expression of many protective pathways such cycle arrest apoptosis. Consequently, this gene is often found disrupted human cancers. Elephants are particularly interesting species for study cancer, virtue their large number divisions long lives yet low incidence cancer. also possess multiple retrogene copies TP53, which have previously been shown induce strong cellular responses damage. However, most previous studies largely focused only on African elephant retrogenes non-native backgrounds. Here we generated CRISPR-Cas9 knockouts all 29 retrogenes, or both combination Asian fibroblasts. We find that while there considerable overlap knockouts, unique enriched both. In particular, exhibit enrichment extracellular suggesting they may play role tumor microenvironment mitigating metastatic growth. small fraction these appear be expressed across variety tissues identify three loci likely driving response. This work shows first time transcriptomic effect within native background establishes foundation future research into relative contributions genes.

Language: Английский

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Walking Through Elephant Cancer Resistance: What it can teach us about elephants, genetics and disease defenses

Journal of Student Research, Journal Year: 2023, Volume and Issue: 12(4)

Published: Nov. 30, 2023

Cancer is a disease that affects the whole animal kingdom, but it does not behave equally in all species. Elephants are one of animals even though have greater number cells their body they present low cancer rate. This phenomenon also known as Peto’s Paradox. Scientists concluded elephants immunity to because genome has extra copies tumor suppressor genes: TP53 and LIF. Even big cancer, still get disease, for example Asian more susceptible getting reproductive tract neoplasia. Exploring this information essential understand how behaves our own genes could help us fight disease. paper review actual knowledge scientific community regarding works elephants, with final goal exploring meaning into understanding genomics develop cure cancer.

Language: Английский

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