Predominant Reliance on Animal Studies
The review primarily synthesizes findings from animal models (e.g., mice, rats, Drosophila) when discussing how exercise attenuates hallmarks of aging. While these models provide mechanistic insights, directly applying these 'novel perspectives' to human health requires significant further validation in human subjects. The paper itself acknowledges this as a limitation.
Lack of Specific Dose-Response Guidance for Humans
The review notes that further research is needed to define optimal exercise parameters (modality, intensity, duration) and identify effective minimum doses and upper safety thresholds for older adults. This indicates that practical, personalized exercise prescriptions based on the reviewed evidence are still under development and not yet fully established.
While comprehensive in covering all 14 hallmarks of aging, the broad scope may lead to less in-depth analysis on specific molecular mechanisms or limitations within each hallmark area, compared to more focused reviews.
The document is a 'Journal Pre-proof,' meaning it has undergone enhancements after acceptance but is not yet the definitive Version of Record. It will undergo additional copyediting, typesetting, and review, which implies that minor errors or changes could still occur before final publication.