Mitochondrial-derived peptides in aging and age-related diseases.

A decline in mitochondrial quality and activity has been associated with normal aging and correlated with the development of a wide range of age-related diseases. Here, we review the evidence that a decline in the levels of mitochondrial-derived peptides contributes to aging and age-related diseases. In particular, we discuss how mitochondrial-derived peptides, humanin and MOTS-c, contribute to specific aspects of the aging process, including cellular senescence, chronic inflammation, and cognitive decline. Genetic variations in the coding region of humanin and MOTS-c that are associated with age-related diseases are also reviewed, with particular emphasis placed on how mitochondrial variants might, in turn, regulate MDP expression and age-related phenotypes. Taken together, these observations suggest that mitochondrial-derived peptides influence or regulate a number of key aspects of aging and that strategies directed at increasing mitochondrial-derived peptide levels might have broad beneficial effects.

Circuit Reorganization Shapes the Developing Human Foveal Midget Connectome toward Single-Cone Resolution.

The human visual pathway is specialized for the perception of fine spatial detail. The neural circuitry that determines visual acuity begins in the retinal fovea, where the resolution afforded by a dense array of cone photoreceptors is preserved in the retinal output by a remarkable non-divergent circuit: cone → midget bipolar interneuron → midget ganglion cell (the "private line"). How the private line develops is unknown; it could involve early specification of extremely precise synaptic connections or, by contrast, emerge slowly in concordance with the gradual maturation of foveal architecture and visual sensitivity. To distinguish between these hypotheses, we reconstructed the midget circuitry in the fetal human fovea by serial electron microscopy. We discovered that the midget private line is sculpted by synaptic remodeling beginning early in fetal life, with midget bipolar cells contacting a single cone by mid-gestation and bipolar cell-ganglion cell connectivity undergoing a more protracted period of refinement.

Mito-Omics and immune function: Applying novel mitochondrial omic techniques to the context of the aging immune system.

Recent advancements in genomic, transcriptomic, proteomic, and metabolomic techniques have prompted fresh inquiry in the field of aging. Here, we outline the application of these techniques in the context of the mitochondrial genome and suggest their potential for use in exploring the biological mechanisms of the aging immune system.