Organelles and Extracellular Vesicles in Bone Aging

Abstract

Bone aging is characterized by a decline in bone mass and structural integrity, increasing fracture and osteoporosis risks in the elderly. This process involves cellular and molecular changes, including impaired osteoblast and osteoclast activity, reduced osteocyte viability, and disrupted intercellular communication within the bone microenvironment. Organelles such as mitochondria, endoplasmic reticulum (ER), lysosomes, and the Golgi apparatus play crucial roles in maintaining cellular homeostasis. During aging, mitochondria show reduced ATP production and increased reactive oxygen species, leading to oxidative stress and impaired bone cell function. ER stress causes accumulation of misfolded proteins, affecting cell survival. Lysosomal dysfunction hampers autophagy, resulting in damaged protein and organelle accumulation. Golgi impairments disrupt protein modification and secretion essential for bone matrix formation. Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in the bone microenvironment by transferring bioactive molecules that influence osteogenesis and osteoclastogenesis. Organelle dysfunctions alter EVs biogenesis and cargo. These changes propagate stress signals and modulate inflammatory responses, which in turn exacerbate bone degeneration. This mini-review summarizes the age-related functional alterations of key organelles in bone cells and elucidates their interactions with EVs. Understanding these relationships provides insights into bone aging pathogenesis and aids in developing therapeutic strategies. Targeting organelle function and modulating EV-mediated communication offer promising approaches to delay or reverse bone aging, improving skeletal health in the aging population.