Dissecting the Molecular and Cellular Pathophysiology of Sarcopenic Obesity in the Elderly

Overview

Ageing is characterised by a change in body composition with a parallel decrease in muscle mass and an increase and central redistribution of fat. When drastically exacerbated, these two processes culminate in a condition known as sarcopenic obesity (SO). SO is characterised by the coexistence of obesity and sarcopenia (i.e. reduced muscle mass and function) and is a growing public health problem in the elderly. The health risks of obesity and sarcopenia act synergistically, maximising the risk of disability of OS. The molecular mechanisms underlying OS are largely unknown. Increased fat mass induces chronic systemic inflammation and alters the profiles of adipokines and hormones, promoting the development of sarcopenia. On the other hand, the reduction in muscle tissue (SM) typical of sarcopenia is characterised by an alteration in the metabolic properties of skeletal muscle with an increase in insulin resistance and a reduction in energy expenditure that favours the accumulation and dysfunction of adipose tissue (AT). The cellular alterations that would seem to underlie OS are: altered autophagy, cellular senescence, epigenetic and mitochondrial alterations and maladaptive activation of intra- and intercellular inflammatory circuits (e.g. cytokines, extracellular vesicles, dysfunctional circulating leukocytes). However, the interconnections between these mechanisms are still unclear. The impact of OS can be dramatic on the health and quality of life of those affected. Therefore, the identification of early biomarkers that can recognise overweight and obese individuals at risk of developing SO is of paramount importance. This would shed light on the heterogeneity of an otherwise homogeneous clinical condition, opening new horizons towards the conscious design of more personalised therapeutic strategies, allowing a more rational use of the limited resources available for the growing elderly population. The study design designed to achieve this aim is a cross-sectional observational study with an additional multicentre procedure lasting two years.

Interventions

• Other clinical evaluation of sarcopenic obesity
  completion of scales and questionnaires, venous blood sampling, muscle ultrasound scan

Primary outcome measures

• Identifying new molecular markers in elderly patients with sarcopenic obesity [Time frame: May 2023- October 2024]

Secondary outcome measures (1)

• Assessing the ability of new markers (identified in the pre-clinical phase of this project) to predict individual disease trajectories [Time frame: May 2023- October 2024]

Eligibility criteria

Inclusion criteria

patients who are candidates for hip surgery

• patients who are candidates for hip surgery
• age ≥ 65 years
• patients able to give consent

healthy subjects

\- healthy subjects from the geriatric cohort studied in 2016-2017 who at that time were: were overweight (25 ≤ BMI < 30 kg/m2) or obese (BMI ≥ 30 kg/m2) but had not yet developed sarcopenia

Exclusion criteria

All partecipants

• unavailability to participate in the study
• inflammatory or neurological myopathies
• acute heart failure
• active cancer

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

Italy · 1 center

• Ospedale San Raffaele — Milan

Identifiers

NCT: NCT06320158 · PNRR-MAD-2022-12376672

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗