Hypotheses on the extended phenotype of the mitochondrion: sex, mortality, and aging DOI Creative Commons

Gordon Irlam

Published: June 19, 2023

How did sex evolve, how is evolutionary stable, why do eukaryotes appear mortal, and age, are all pressing questions. This paper presents a mitochondrial perspective on the evolution of eukaryotic cell that appears capable answering these Rather than viewing mitochondrion as passive entity taken up by an archaeal host remains in driving seat, mitochondria viewed key force eukaryogenesis. The proto-mitochondrion presumed to have manipulated its engage order replicate itself more beneficial environment. process hypothesized still be operating today result mitochondrion's continued production reactive oxygen species (ROS). specific ROS intentional mechanism cause organism ultimately die. Faced with mortality, if wishes pass nuclear genes it will typically means resetting age. Eukaryotic instead reproduced parthenogenetically would find themselves out-competed sexual due reassortment comes sex. genome benefits via kin selection from death increased ability adapt changing environment shortened time between successive generations. resulting model explaining seeming intentionality many age-related diseases, provides high level theoretical framework for better understanding them.

Language: Английский

Stress, diet, exercise: Common environmental factors and their impact on epigenetic age DOI Creative Commons
Fedor Galkin, Olga Kovalchuk, Diana Koldasbayeva

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 88, P. 101956 - 101956

Published: May 20, 2023

Epigenetic aging clocks have gained significant attention as a tool for predicting age-related health conditions in clinical and research settings. They enabled geroscientists to study the underlying mechanisms of assess effectiveness anti-aging therapies, including diet, exercise environmental exposures. This review explores effects modifiable lifestyle factors' on global DNA methylation landscape, seen by clocks. We also discuss through which these factors contribute biological provide comments what findings mean people willing build an evidence-based pro-longevity lifestyle.

Language: Английский

Citations

54
Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages DOI Creative Commons
Anna Csiszár, Anna Ungvari, Roland Patai

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 5103 - 5132

Published: April 19, 2024

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They prevalent in the aging population, with multiple often being observed given individual. closely associated accelerated cognitive decline and increasingly recognized key contributors to pathogenesis vascular impairment dementia (VCID) Alzheimer's (AD). This review paper delves into hypothesis that atherosclerosis, age-related large disease, extends its influence microcirculation, thereby contributing development progression CSVD, specific focus on CMHs. We explore concept continuum, bridging macrovascular pathologies like atherosclerosis microvascular abnormalities characteristic CSVD. posit same risk factors precipitating vessels (i.e., atherogenesis), primarily oxidative stress inflammatory pathways, similarly instigate aging. Accelerated leads increased fragility, which turn predisposes formation The presence hypertension amyloid pathology further intensifies this process. comprehensively overview current body evidence supporting interconnected hypothesis. Our includes examination epidemiological data, provides insights prevalence impact context Furthermore, we shared mechanisms between aging, atherogenesis, particularly focusing how these intertwined processes contribute genesis By highlighting role pathophysiology CMHs, seeks enhance understanding CSVD links systemic disorders. aim is provide could inform future therapeutic approaches research directions realm neurovascular health.

Language: Английский

Citations

22
Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health DOI Creative Commons
Mónika Fekete, Andrea Ceglédi,

Ágnes Szappanos

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Language: Английский

Citations

2
Tricarboxylic Acid Cycle Intermediates and Individual Ageing DOI Creative Commons
Natalia Kurhaluk

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 260 - 260

Published: Feb. 22, 2024

Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components these effects postulated to be related the energy supply by tricarboxylic acid (TCA) cycle intermediates free radical production processes. article presents several theories ageing clinical descriptions top markers ageing, which define in different categories; additionally, their interactions with age-related changes diseases α-ketoglutarate (AKG) succinate SC formation metabolism pathological states explained. review describes convincingly differences mitochondrial characteristics animals, levels (high low) physiological reactivity functional systems state regulatory providing oxygen-dependent Much attention is given crucial role AKG cells amino synthesis, epigenetic regulation, cell stemness, differentiation, as well associated development conditions and, particular, cancer cells. Another goal was address issue terms individual reactivity. also demonstrated Krebs key component cellular closely various pathologies, such cancer, type 2 diabetes, cardiovascular or neurodegenerative where mTOR pathway plays role. provides postulates postischaemic phenomena an organism demonstrates dependence accelerated pathology on studies species (roundworm Caenorhabditis elegans, Drosophila, mice, humans used models). The findings suggest that this approach may useful show metabolites involved abnormalities thus induce reprogramming contributes senile phenotype degenerative diseases. compounds particularly important when considering mechanisms connected initial able initiate programmed depending intensity oxygen consumption, peculiarities, behavioural reactions.

Language: Английский

Citations

13
Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians DOI Creative Commons
Ceereena Ubaida‐Mohien, Ruin Moaddel, Sally Spendiff

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Physical function declines with aging, yet there is considerable heterogeneity, some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical we performed proteomics, targeted metabolomics, and kynurenine-focused metabolomic analyses on serum specimens from three groups of octogenarians: High-functioning master athletes (HF, n = 16), healthy normal-functioning non-athletes (NF, 12), lower functioning (LF, 11). Higher performance status was associated evidence consistent with: Lower levels circulating proinflammatory markers, as well unperturbed tryptophan metabolism, the normal kynurenic pathway; higher lysophosphatidylcholines that have been previously better mitochondrial oxidative capacity; activity integrated stress response; SASP protein members; proteins reflect neurodegeneration/denervation. Extending observations previous studies focused biomarkers aging predict poor function, our findings show many same exhibit attenuated changes in those who maintain a function. Because cross-sectional nature this study, results should be interpreted caution, bidirectional causality, where behavior both cause outcome differences biomarker changes, remains possible interpretation.

Language: Английский

Citations

0
Synbiotic pineapple beverage increases life span in Caenorhabditis elegans, ameliorates cognitive impairment, and restores gut microbiome diversity in D-galactose-induced aged C57BL/6 mice DOI

Neelam Anil Revankar,

Siddaraju Anusha,

Muthukumar Serva Peddha

et al.

Biogerontology, Journal Year: 2025, Volume and Issue: 26(3)

Published: May 3, 2025

Language: Английский

Citations

0
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies DOI Creative Commons
Vharoon Sharma Nunkoo,

Alexander Cristian,

Anamaria Jurcău

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2540 - 2540

Published: Nov. 7, 2024

The impressive achievements made in the last century extending lifespan have led to a significant growth rate of elderly individuals populations across world and an exponential increase incidence age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, neurodegenerative diseases. To date, geroscientists identified 12 hallmarks aging (genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, impaired macroautophagy, mitochondrial dysfunction, nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, well more aggressive approaches cell-based therapies. side effects seriously limit use these drugs. However, since rejuvenation is dream mankind, future research expected improve tolerability available drugs highlight novel strategies. In meantime, medical community, healthcare providers, society should decide when start treatments how tailor them individually.

Language: Английский

Citations

3
Steroidogenic Acute Regulatory Protein Mediated Variations of Gender-Specific Sex Neurosteroids in Alzheimer’s Disease: Relevance to Hormonal Imbalance DOI Creative Commons
Pulak R. Manna, Shengping Yang, Claudio Manna

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 169, P. 105969 - 105969

Published: Dec. 3, 2024

Language: Английский

Citations

0
Hypotheses on the extended phenotype of the mitochondrion: sex, mortality, and aging DOI Creative Commons

Gordon Irlam

Published: June 19, 2023

How did sex evolve, how is evolutionary stable, why do eukaryotes appear mortal, and age, are all pressing questions. This paper presents a mitochondrial perspective on the evolution of eukaryotic cell that appears capable answering these Rather than viewing mitochondrion as passive entity taken up by an archaeal host remains in driving seat, mitochondria viewed key force eukaryogenesis. The proto-mitochondrion presumed to have manipulated its engage order replicate itself more beneficial environment. process hypothesized still be operating today result mitochondrion's continued production reactive oxygen species (ROS). specific ROS intentional mechanism cause organism ultimately die. Faced with mortality, if wishes pass nuclear genes it will typically means resetting age. Eukaryotic instead reproduced parthenogenetically would find themselves out-competed sexual due reassortment comes sex. genome benefits via kin selection from death increased ability adapt changing environment shortened time between successive generations. resulting model explaining seeming intentionality many age-related diseases, provides high level theoretical framework for better understanding them.

Language: Английский

Citations

0