Mitochondrial-to-nuclear communication in aging: an epigenetic perspective

Mito-nuclear communication plays an integral role in cellular homeostasis and aging. Mitochondrial metabolites are substrates or mediators of epigenetic modifications. Mitochondrial-to-nuclear stress signals modulate lifespan via epigenetic regulations. Age-associated changes in mitochondria are closely involved in aging. Apart from the established roles in bioenergetics and biosynthesis, mitochondria are signaling organelles that communicate their fitness to the nucleus, triggering transcriptional programs to adapt homeostasis stress that is essential for organismal health and aging. Emerging studies revealed that mitochondrial-to-nuclear (mito-nuclear) communication via altered levels of mitochondrial metabolites or stress signals causes various epigenetic changes, facilitating efforts to maintain homeostasis and affect aging. Here, we summarize recent studies on the mechanisms by which mito-nuclear communication modulates epigenomes and their effects on regulating the aging process. Insights into understanding how mitochondrial metabolites serve as prolongevity signals and how aging affects this communication will help us develop interventions to promote longevity and health. Age-associated changes in mitochondria are closely involved in aging. Apart from the established roles in bioenergetics and biosynthesis, mitochondria are signaling organelles that communicate their fitness to the nucleus, triggering transcriptional programs to adapt homeostasis stress that is essential for organismal health and aging. Emerging studies revealed that mitochondrial-to-nuclear (mito-nuclear) communication via altered levels of mitochondrial metabolites or stress signals causes various epigenetic changes, facilitating efforts to maintain homeostasis and affect aging. Here, we summarize recent studies on the mechanisms by which mito-nuclear communication modulates epigenomes and their effects on regulating the aging process. Insights into understanding how mitochondrial metabolites serve as prolongevity signals and how aging affects this communication will help us develop interventions to promote longevity and health. a molecule that carries energy within cells. ATP consists of adenine, ribose, and three groups of phosphoric acid, which release energy during hydrolysis. a series of protein complexes that transfer electrons from electron donors to electron acceptors via redox reactions and couple this electron transfer with the transfer of protons across a membrane. a protective transcriptional response used to promote organelle-specific proteostasis during mitochondrial dysfunction. a molecule (secreted protein, peptides, or others) produced and secreted from cells experiencing mitochondrial stress, eliciting an organismal mitochondrial stress response in distal tissues that have not been directly affected by the stress stimulus. comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. a metabolic pathway in which cells use enzymes to release the chemical energy stored within the nutrients through oxidation in order to produce ATP. by-products of cellular metabolism, primarily in the mitochondria; oxygen-containing radicals that are capable of independent existence with one or more unpaired electrons, which is essential for cell physiology and participates in many pathological processes. a cyclic series of enzymatic reactions occurring in the mitochondrial matrix, through which organisms produce energy.