scholarly journals Mitonuclear interactions alter sex-specific longevity in a species without sex chromosomes

2021 ◽  
Vol 288 (1962) ◽  
Author(s):  
Ben A. Flanagan ◽  
Ning Li ◽  
Suzanne Edmands
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Sex Differences ◽  
Sex Chromosomes ◽  
Mitochondrial Function ◽  
F1 Hybrid ◽  
Young Females ◽  
Mitochondrial Haplotypes ◽  
Age Related ◽  
Adult Sex Ratio

Impaired mitochondrial function can lead to senescence and the ageing phenotype. Theory predicts degenerative ageing phenotypes and mitochondrial pathologies may occur more frequently in males due to the matrilineal inheritance pattern of mitochondrial DNA observed in most eukaryotes. Here, we estimated the sex-specific longevity for parental and reciprocal F1 hybrid crosses for inbred lines derived from two allopatric Tigriopus californicus populations with over 20% mitochondrial DNA divergence. T. californicus lacks sex chromosomes allowing for more direct testing of mitochondrial function in sex-specific ageing. To better understand the ageing mechanism, we estimated two age-related phenotypes (mtDNA content and 8-hydroxy-20-deoxyguanosine (8-OH-dG) DNA damage) at two time points in the lifespan. Sex differences in lifespan depended on the mitochondrial and nuclear backgrounds, including differences between reciprocal F1 crosses which have different mitochondrial haplotypes on a 50 : 50 nuclear background, with nuclear contributions coming from alternative parents. Young females showed the highest mtDNA content which decreased with age, while DNA damage in males increased with age and exceed that of females 56 days after hatching. The adult sex ratio was male-biased and was attributed to complex mitonuclear interactions. Results thus demonstrate that sex differences in ageing depend on mitonuclear interactions in the absence of sex chromosomes.

Late onset administration of oral antioxidants prevents age-related loss of motor co-ordination and brain mitochondrial DNA damage

1998 ◽  
Vol 29 (6) ◽  
pp. 617-623 ◽  
Author(s):  
F.V. Pallardó ◽  
M. Asensi ◽  
J. García de la Asunciôn ◽  
V. Antón ◽  
A. Lloret ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Late Onset ◽  
Mitochondrial Dna Damage ◽  
Age Related

Age-Related Sex Differences in Glutathione Peroxidase and Oxidative DNA Damage in a Healthy Mexican Population

2010 ◽  
Vol 19 (5) ◽  
pp. 919-926 ◽  
Author(s):  
Víctor Manuel Mendoza-Núñez ◽  
Ada Beristain-Pérez ◽  
Silvia Patricia Pérez-Vera ◽  
Mario A. Altamirano-Lozano
Keyword(s):  
Dna Damage ◽  
Sex Differences ◽  
Glutathione Peroxidase ◽  
Oxidative Dna Damage ◽  
Mexican Population ◽  
Age Related

scholarly journals TMIC-17. ASTROCYTE SENESCENCE CONTRIBUTES TO SEX DIFFERENCES IN THE AGE-RELATED INCREASE IN GLIOBLASTOMA INCIDENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi250-vi251
Author(s):  
Lauren Broestl ◽  
Jasmin Sponagel ◽  
Gina Rhee ◽  
Lucia Grandison ◽  
Najla Kfoury ◽  
...  
Keyword(s):  
Dna Damage ◽  
Sex Differences ◽  
Incidence Rates ◽  
Paracrine Signaling ◽  
Male And Female ◽  
Cycle Arrest ◽  
Age Related ◽  
Anti Cancer ◽  
A Cell ◽  
Tumor Types

Abstract Incidence rates for glioblastoma increase exponentially with age in a sex-specific manner, with a steeper increase observed in men. This suggests that age may be a more significant factor in promoting male tumors than female tumors. Drivers in the age-related cancer increase include both the accumulation of DNA damage and microenvironment changes, specifically an increase in the number of senescent cells. Cellular senescence comprises two distinct components – a cell cycle arrest program that prevents proliferation of mutated cells and acts as a potent anti-cancer mechanism, and a paracrine signaling component that can have both pro- and anti-tumorigenic properties. The contribution of senescence to brain tumor incidence and outcome is currently unknown; additionally, no research has been done on whether there are sex differences in mechanisms of senescence induction or in the secretory phenotype of senescent cells. Using both wildtype astrocytes and a glioblastoma model, we show that female cells have a lower threshold for senescence induction in response to oxidative stress, telomere shortening, and DNA damage, and that sex differences in senescence induction in response to DNA damage are in part mediated by differences in the regulation of p21. In addition, we show that male and female senescent astrocytes differ in their secretory phenotypes. Male senescent astrocytes secrete more tumor promoting factors, and conditioned media from male but not female senescent astrocytes promotes tumor cell proliferation. These findings provide a potential explanation for sex differences in glioblastoma incidence rates. Achieving a better understanding of mechanisms of senescence and how they differ in male and female cells could advance development of senescence directed therapies and potentially improve cancer treatment for a range of tumor types.

Influence of Lecithin on Mitochondrial DNA and Age-Related Hearing Loss

2002 ◽  
Vol 127 (3) ◽  
pp. 138-144 ◽  
Author(s):  
Michael D. Seidman ◽  
Mumtaz J. Khan ◽  
Wen Xue Tang ◽  
Wayne S. Quirk
Keyword(s):  
Flow Cytometry ◽  
Hearing Loss ◽  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
High Energy ◽  
Membrane Potentials ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Age Related

;OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA4834) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.

scholarly journals Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage

2004 ◽  
Vol 124 (0) ◽  
pp. 16-24 ◽  
Author(s):  
Michael Seidman ◽  
Nadir Ahmad ◽  
Dipa Joshi ◽  
Jake Seidman ◽  
Sujatha Thawani ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Hearing Loss ◽  
Mitochondrial Dna ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Dna Damage ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Mitochondrial DNA Damage as a Potential Mechanism for Age-Related Macular Degeneration

2010 ◽  
Vol 51 (11) ◽  
pp. 5470 ◽  
Author(s):  
Pabalu P. Karunadharma ◽  
Curtis L. Nordgaard ◽  
Timothy W. Olsen ◽  
Deborah A. Ferrington
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Potential Mechanism ◽  
Mitochondrial Dna Damage ◽  
Age Related

scholarly journals HIV-1 and HIV-1-Tat Induce Mitochondrial DNA Damage in Human Neurons

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Darbinian N ◽  
Darbinyan A ◽  
Merabova N ◽  
Selzer ME ◽  
Amini S
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Neurodegenerative Disorders ◽  
Accelerated Ageing ◽  
Mtdna Damage ◽  
Mitochondrial Dna Damage ◽  
Age Related ◽  
Human Neurons ◽  
Hiv 1

Introduction: Mitochondrial dysregulation is a key event in HIV-1 infection. Recent studies have suggested that age-related neurodegenerative disorders are associated with increased mitochondrial DNA (mtDNA) damage. As accelerated ageing was found in HIV-1 patients, we hypothesized that HIV-1 infection or HIV-1 proteins can lead to mtDNA damage. Unrepaired mtDNA impairs mitochondrial function, which can lead to oxidative stress and cell death. Investigations of mechanisms of mtDNA damage are limited by the lack of available human models.

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