Leader: Alessandro Laviano (SAPIENZA) ; Other collaborator(s): Francesca Cecchi (UNIFI); RTDA PNRR TBA, (UNICATT); Patrizia Rovere Querini (UNISR)
Nutritional status can be considered a marker of aging, and declining muscle mass a marker of accelerated aging. Exploring the interplay between nutrition and muscle mass loss may help predict disability. Trajectories in muscle changes during exacerbation of chronic diseases may predict a future functional decline. The response to nutritional interventions on muscle mass may predict the success of conventional intervention strategies on outcomes. Milestones are 1) analysis (post-hoc) of nutritional status as a modifier of the relationship between muscle loss and outcomes in patients; 2) inclusion of tailored nutrition in the stratified care pathways of the multimorbid patient; 3) pilot studies for nutritional intervention in the prevention of disability worsening.
Brief description of the activities and of the intermediate results: Contacts are being made with the Home Artificial Nutrition team at ASL Roma1, in order to verify the interest in pursuing such study and whether the available database includes the necessary biochemical and nutritional information. Considering that patients receiving home artificial nutrition appear to represent quite a selected group of patients, with limited possibility of translation to other groups of patients, contacts are being made with general practitioners to evaluate the possibility to assess the predictive role of biological age and nutritional status on outcomes. Assessment of the completeness of the selected database from which deriving the possible association/correlation of nutritional status/body composition with biological age.
Appreciation that in many available database, the biochemical markers needed to determine biological age according to Levine’s PhenoAge are not all available. Contact with centers managing databases to assess whether the missing information is retrievable. Contact with Prof. Han Ping Shi (Capital Medical University, Beijing, China) to develop and validate a simplified version of the PhenoAge clock, to be used on those database in which information to derive biological age is missing.
Drafting of the paper on Digital HL among older adults.
Main policy, industrial and scientific implications: Better definition of targets that could interfere with ageing trajectories. Identification of the possibility of using senolytics/senomorphic in adjunct to nutritional support to prevent frailty of aging.
During this trimester, the Sapienza, Rome/Capital University, Beijing research group secured access to 2 large databases, one of patients with cancer (n=2853) and the other of healthy individuals (n=4477). The group decided the research questions to be addressed by the analysis of the databases:
1. Is there any association/correlation between muscle mass and function and biological age as assessed by PhenoAge clock?
2. When biological age as assessed by PhenoAge clock is introduced in the predictive equations for mortality risk, is sensitivity improved?
Considering that biological age is a modifiable risk factor, the results of this analysis would help in implementing preventive and treatment strategies aiming at improving prognosis.
The analysis of the databases started in June 2024.
When the statistical analysis of the databases was completed, the following results were obtained:
1. Biological age is significantly and negatively associated with muscle mass and function, suggesting that it is a reliable marker of body composition and function, likely more rapidly reacting to interventions
2. Biological age adjusted indicators demonstrated higher sensitivity and specificity in predicting mortality in the general population and in patients with cancer.
These data, which confirm the research hypothesis, are now being used to prepare a comprehensive manuscript to be submitted to an international scientific journal.
During the period October-December 2024, the project for validating the hypothesis that nutritional status, and especially body composition, are markers of biological age and therefore allow the assessment of the health status of individuals, was finalized. To this end, the calculations obtained so far on 2 large databases, NHANES (USA, healthy subjects) and INSCOC (China, cancer patients), were verified, which confirm that biological age is inversely correlated with muscle mass and strength. Furthermore, correcting known clinical risk factors (e.g., HDL and muscle strength) for biological age improves the predictive capacity. The manuscript was therefore prepared now sent to a scientific journal for possible publication.
Dissemination