Energy Metabolism Focused Analysis of Sexual Dimorphism in Biological Aging and Hypothesized Sex-specificity in Sirtuin Dependency

Salekeen, Rahagir; Diaconeasa, Amalia Gabriela; Billah, Morsaline; Islam, Kazi Mohammed Didarul

doi:10.1016/j.mito.2021.07.007

Cited by 4 publications

(3 citation statements)

References 113 publications

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“…A hypothetical model has been proposed in which advantageous effects promoted by SIRTs could be presented in a sex-nonspeci c manner. However, after reaching reproductive maturity, it has been hypothesized that SIRT dependency in modulating metabolic networks are evolutionarily decoupled from female longevity [94]. In this work, the neurodegenerative process differentially impacts on SIRT pro le depending on disease, sex, and olfactory-related areas, affecting the global acetylation/deacetylation machinery of the human brain.…”

Section: Perspective and Signi Cancementioning

confidence: 89%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Cartas-Cejudo

Lachén-Montes

Ferrer

et al. 2022

Preprint

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Background: Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated to olfactory dysfunction. Methods: SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 postmortem olfactory tracts (OT) derived from non-demented (n=6F/11M), AD (n=4F/13M) and PD (n=7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas. Results: 327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men respectively (35 DEPs in common). Respect to PD, 198 DEPs were identified in PD women whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory-entorhinal-amygdaloid axis, evidencing disease- sex- and brain structure-dependent changes in olfactory protein acetylation. Conclusions: Alteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.

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Section: Perspective and Signi Cancementioning

confidence: 89%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Cartas-Cejudo

Lachén-Montes

Ferrer

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…A hypothetical model has been proposed in which advantageous effects promoted by SIRTs could be presented in a sex-nonspecific manner. However, after reaching reproductive maturity, it has been hypothesized that SIRT dependency in modulating metabolic networks are evolutionarily decoupled from female longevity [ 95 ]. In this work, the neurodegenerative process differentially impacts on SIRT profile depending on disease, sex, and olfactory-related areas, affecting the global acetylation/deacetylation machinery of the human brain.…”

Section: Perspective and Significancementioning

confidence: 99%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

et al. 2023

View full text Add to dashboard Cite

Background Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated with olfactory dysfunction. Methods SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 post-mortem olfactory tracts (OT) derived from controls with no known neurological history (n = 6F/11M), AD (n = 4F/13M) and PD (n = 7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas. Results 327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men, respectively (35 DEPs in common). With respect to PD, 198 DEPs were identified in PD women, whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory–entorhinal–amygdaloid axis, evidencing disease-, sex- and brain structure-dependent changes in olfactory protein acetylation. Conclusions Alteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.

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“…In addition, SIRTs exhibit a variety of catalytic activities, and these pleiotropic enzyme activities play important roles in silencing regulatory proteins, maintaining genomic integrity, regulating metabolic homeostasis, and promoting organism longevity ( Salekeen et al, 2021 ). SIRTs share an NAD + -binding catalytic domain and act specifically on different substrates based on the biological processes in which they are involved.…”

Section: Sirts In the Hdac Familymentioning

confidence: 99%

Sirtuins—Novel Regulators of Epigenetic Alterations in Airway Inflammation

Liu

2022

Front. Genet.

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Histone modification is an important epigenetic alteration, and histone deacetylases are involved in the occurrence and development of various respiratory diseases. Sirtuins (SIRTs) have been demonstrated to play an important role in the formation and progression of chronic inflammatory diseases of the respiratory tract. SIRTs participate in the regulation of oxidative stress and inflammation and are related to cell structure and cellular localization. This paper summarizes the roles and mechanisms of SIRTs in airway inflammation and describes the latest research on SIRT modulators, aiming to provide a theoretical basis for the study of potential epigenetic alteration-inducing drug targets.

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Energy Metabolism Focused Analysis of Sexual Dimorphism in Biological Aging and Hypothesized Sex-specificity in Sirtuin Dependency

Cited by 4 publications

References 113 publications

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

Sirtuins—Novel Regulators of Epigenetic Alterations in Airway Inflammation

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