Adenosine receptor signaling loss is linked to age-related diseases that impact the skin, musculoskeletal system, and vasculature, underscoring adenosine's critical role in cellular function.

Extracellular adenosine is a vital signaling molecule primarily produced through the dephosphorylation of adenine nucleotides, especially ATP, at the cell surface.

With aging, the expression of enzymes CD73 and CD39, which regulate extracellular adenosine production, decreases significantly, influenced by estrogen levels.

Aging leads to diminished mitochondrial function and ATP production, resulting in reduced adenosine levels, which adversely affects cellular and tissue functions.

A lack of proper ATP hydrolysis to adenosine can result in tissue injury, as seen in patients deficient in CD73, leading to vascular tissue calcification.

The aging process is associated with chronic conditions that affect various systems, including musculoskeletal, cardiovascular, and immune systems, driven by factors such as genomic damage and mitochondrial dysfunction.

Increased extracellular adenosine levels can arise from genetic disorders like adenosine deaminase deficiency or from pharmacological agents that inhibit ATP transport.

The article suggests that age-related alterations in purine metabolism, particularly in adenosine signaling, may contribute to aging and highlight potential new treatment targets for musculoskeletal issues.

The aging population in the United States is expected to rise significantly, from 14.5% in 2014 to 23.5% by 2060, with projections indicating around 77 million individuals aged 65 or older by 2030.

The conclusion of the article emphasizes the potential for targeting adenosine receptors in therapeutic strategies for aging-related conditions and sheds light on the mechanisms underlying aging and chronic inflammation.