NEURO NUGGETS

BY DR MOHD WAEL

Dr Wael MY Mohamed is with the Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University Malaysia( IIUM).

BY DR WAEL

Healthy Longevity Medicine seeks to optimise both lifespan and health span by targeting the biological processes of ageing. Building upon discoveries in gerosciences, it aims to translate insights from model organisms into human applications, bridging basic research with clinical and public health strategies.

Understanding societal attitudes toward ageing, health span, and related interventions is essential. Countries like Malaysia, now an entirely aged society, exemplify both the opportunities and challenges of population ageing.

These include healthcare demands, quality-of-life concerns, and social adaptation. Unique considerations also arise in subgroups such as transgender individuals undergoing long-term hormone therapy and expatriates facing distinctive physical and psychological adjustments.

At the molecular level, ageing is characterised by altered gene expression, loss of proteostasis, and dysregulated nutrientsensing pathways. Central to these processes are redox signalling molecules, particularly reactive oxygen species( ROS) and hydrogen sulfide( H₂S). Once viewed solely as damaging by-products, these molecules are now recognised as vital mediators of longevity.

Modest increases in ROS and H₂S levels can extend lifespan in model organisms, influencing proteins through cysteine modifications. Intriguingly, pro-longevity interventions, such as dietary restriction and germline removal, simultaneously upregulate ROS and H₂S, suggesting a complex, interconnected signalling network.

A NEW ERA IN MEDICINE

Recent advances in chemoproteomics have expanded our understanding of the redox proteome, highlighting the need to determine which specific cysteine

modifications directly influence ageing and lifespan. This knowledge could pave the way for novel therapeutic strategies to delay age-related decline.

Measurable biological, physiological, or psychological parametres are critical tools for tracking ageing processes. They enable the early detection of accelerated ageing, the assessment of interventions, and the evaluation of preventive strategies, such as lifestyle modifications and geroprotective drugs.

However, challenges remain, including variability among individuals, lack of standardised protocols, and the tendency of current healthcare systems to prioritise reactive rather than preventive approaches.

To address these issues, biomarkers are now classified into five categories: clinical, functional, molecular, omics-based, and digital. A robust biomarker must reliably change with age, predict mortality risk more accurately than chronological age, detect the early stages of age-related diseases, and be minimally invasive.

Given the complexity of ageing, no single biomarker can capture the entire process. The most promising approach is to combine multiple markers into composite panels and integrate them into explainable artificial intelligence( XAI) models. These multidimensional systems can predict individual ageing trajectories, guide personalised interventions, and optimise clinical trial designs.

Looking forward, the field aims to develop " ageing clocks " for specific organs and systems, enabling precise monitoring and management of age-related changes. Future progress will rely on large-scale longitudinal studies, advanced biobanking, and population-specific data integration, ultimately ushering ageing research into a new era of precision longevity medicine.

BIOMARKERS TO LONGEVITY

Nonetheless, it is crucial to recognise that both individual markers and their composite implementations need a shift from population assessments to really personalised evaluations. This is a straightforward example pertaining to the

interpretation of the T4 level: We propose that the patient ' s value is 10 units, with a reference range of 5-12 for those over one year of age; thus, the present conclusion is that it is within normal limits.

Is this level ideal for this specific patient? Does this number for this individual indicate molecular alterations and serve as a forerunner to future physiological disruptions, perhaps resulting in faster bodily wear and ageing?

To gain a more profound interpretation, it is essential to employ more comprehensive methodologies that enable the examination of the parameter within the context of other indicators, considering the interactions between their respective levels.

The comprehensive interpretation may be facilitated by a wide array of indicators and the development of nonlinear models adept at catching intricate patterns, such as machine learning methods, particularly neural networks. The practical use of " ageing clocks " in contemporary biomedicine is advancing in two primary ways.

These methods allow the accurate identification of individuals exhibiting indicators of accelerated ageing, who are predisposed to a heightened risk of acquiring certain age-related disorders.

The Arterial Indices, GrimAge, and EchoAGE systems have significant predictive value for cardiovascular illnesses; Horvath ' s clock model pertains to neurodegenerative disorders; and the PhenoAge system relates to endocrine and metabolic conditions.

The utilisation of these tools for evaluating potential geroprotective compounds is equally significant, as demonstrated by the findings of a controlled clinical trial in which a three-month regimen of a biologically active supplement containing fir terpenes resulted in an average reduction of arterial age( assessed via the Arterial Indices system) by 2.5 years.

Take-home message: Ageing is inevitable, but suffering is optional— think of biomarkers as your body ' s " check engine " light. The trick is to tune up early, before you end up needing a complete body overhaul!- The HEALTH