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

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Energy Metabolism Focused Analysis of Sexual Dimorphism in Biological Aging and Hypothesized Sex-specificity in Sirtuin Dependency
Mitochondrion ( IF 3.9 ) Pub Date : 2021-07-29 , DOI: 10.1016/j.mito.2021.07.007
Rahagir Salekeen ₁ , Amalia Gabriela Diaconeasa ₂ , Md Morsaline Billah ₁ , Kazi Mohammed Didarul Islam ₁

Affiliation

The process of biological aging or senescence refers to the gradual loss of homeostasis and subsequent loss of function – leading to higher chances of mortality. Many mechanisms and driving forces have been suggested to facilitate the evolution of a molecular circuit acting as a trade-off between survival and proliferation, resulting in senescence. A major observation on biological aging and longevity in humans and model organisms is the prevalence of significant sexual divergence in the onset, mechanisms and effects of aging associated processes. In the current account, we describe possible mechanisms by which aging, sex and reproduction are evolutionarily intertwined in order to maintain systemic energy homeostasis. We also interrogate existing literature on the sexual dimorphism of genetic, cellular, metabolic, endocrine and epigenetic processes driving cellular and systemic aging. Subsequently, based on available evidence, we propose a hypothetic model of sex-limited decoupling of female longevity from sirtuins, a major family of regulator proteins of the survival-proliferation trade-off. We also provide necessary considerations to be made in order to test the hypothesis and explore the physiological and therapeutic implications of this decoupling event in male and female longevity after reaching reproductive maturity.

Hypothesis Statement

Sirtuins provide survival benefits in a sex-nonspecific manner but the dependency on sirtuins in driving metabolic networks after reaching reproductive maturity is evolutionarily decoupled from female longevity.

中文翻译：

能量代谢聚焦分析生物衰老中的性二态性和假设的 Sirtuin 依赖的性别特异性

生物老化或衰老的过程是指体内平衡逐渐丧失和随后的功能丧失——导致更高的死亡机会。已经提出了许多机制和驱动力来促进分子回路的进化，作为生存和增殖之间的权衡，从而导致衰老。关于人类和模式生物的生物衰老和寿命的一个主要观察结果是，在衰老相关过程的发生、机制和影响方面普遍存在显着的性别差异。在当前帐户中，我们描述了衰老、性和生殖在进化上相互交织以维持系统能量稳态的可能机制。我们还询问有关遗传、细胞、代谢、内分泌和表观遗传过程驱动细胞和全身老化。随后，基于现有证据，我们提出了一个假设性模型，即女性寿命与 sirtuins 的性别限制脱钩，sirtuins 是生存 - 增殖权衡的主要调节蛋白家族。我们还提供了必要的考虑因素，以检验该假设并探索这种脱钩事件对达到生殖成熟后男性和女性寿命的生理和治疗意义。