Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age

Abstract

Current research on human aging has largely been guided by the milestone paper “hallmarks of aging,” which were first proposed in the seminal 2013 paper by Lopez‐Otin et al. Most studies have focused on one aging hallmark at a time, asking whether the underlying molecular perturbations are sufficient to drive the aging process and its associated phenotypes. More recently, researchers have begun to investigate whether aging phenotypes are driven by concurrent perturbations in molecular pathways linked to not one but to multiple hallmarks of aging and whether they present different patterns in organs and systems over time. Indeed, preliminary results suggest that more complex interactions between aging hallmarks must be considered and addressed, if we are to develop interventions that successfully promote healthy aging and/or delay aging‐associated dysfunction and diseases. Here, we summarize some of the latest work and views on the interplay between hallmarks of aging, with a specific focus on mitochondrial dysfunction. Indeed, this represents a significant example of the complex crosstalk between hallmarks of aging and of the effects that an intervention targeted to a specific hallmark may have on the others. A better knowledge of these interconnections, of their cause‐effect relationships, of their spatial and temporal sequence, will be very beneficial for the whole aging research field and for the identification of effective interventions in promoting healthy old age.

Healthy aging: Linking causal mechanisms with holistic outcomes

“…Identifying efficacious interventions that are broadly acceptable, cost‐effective, and scalable remains the coin of the realm for geroscientists. In this special issue, Li and colleagues ( 2023 ) suggest a more nuanced strategy for designing interventions aimed at promoting healthy aging. Instead of targeting a specific aging hallmark with associated phenotypes, pathways effecting multiple hallmarks of aging should be targeted (e.g., mitochondrial dysfunction), positing that interventions targeting key hallmarks could have cascading effects across the aging process.…”

Melatonin Exerts Prominent, Differential Epidermal and Dermal Anti-Aging Properties in Aged Human Eyelid Skin Ex Vivo

“…Mitochondrial dysfunction plays a crucial role in skin aging [33,63,[73][74][75], leading us to also investigate the impact of melatonin on the expression of the key mitochondrial proteins cytochrome c oxidase I (MTCO-1) and mitochondrial transcription factor (TFAM), which control mitochondrial biogenesis and DNA synthesis [21][22][23]. We also examined voltage-dependent anion channel VDAC/Porin expression, as a useful screening marker for mitochondrial abundance.…”