Reference
Fried, L.P., Cohen, A.A., Xue, QL. et al. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging 1, 36–46 (2021). https://doi.org/10.1038/s43587-020-00017-z
Abstract
The latest evidence in scientific research highlights the need for a new concept of frailty: it is not the sum of the patient’s diseases and comorbidities (as previously believed), but a complex multisystemic dysregulation, which drastically decreases the body’s dynamic adaptation skills. This “new model” of frailty might appear as a clearly defined clinical state, or become apparent in times of acute stress.
Background
As we grow older, our body becomes increasingly frail. This frailty, however, is not merely an accumulation of deficits caused by multiple diseases and comorbidities. This condition is actually characterized by many underlying biological mechanisms, which cause a synergic deterioration of the body’s adaptative systems. Above a certain stress threshold (unique for every patient), the body starts to show a clear clinical presentation of physical frailty.
Recent pilot studies have highlighted the existence of strong connections between physical frailty and the dysregulation of two important macro-systems of the body:
- the metabolic system, which includes both energy production efficiency (glucose-related systems and energy-regulatory hormones) and energy consumption (mostly musculoskeletal and mitochondrial systems);
- the stress-responsive system, whose most important component is the immunity system (determined by measuring PCR, IL-6, and white blood cells).
More specifically, evidence shows higher levels of glucose and insulin in the blood samples of frail patients, compared to non-frail patients of the same age. Frail patients also show a dysregulation of the phosphocreatine metabolism, ACTH systemic response, immunity response to infections and vaccines, and an increased incidence of orthostatic hypotension.
On a clinical level, frailty can be identified when the patient presents at least 3 of the following 5 symptoms: weakness, slow walking speed, low physical activity, fatigue or exhaustion, unintentional weight loss.
Study parameters
The study was conducted on a female population aged between 70 and 80. It assessed 8 frailty-related markers (both clinical and laboratorial): IL-6 to study the inflammatory system; hemoglobin to control anemia; IGF-1, DHEAS, and A1C hemoglobin to observe the endocrine system; micronutrient deficiency and body adiposity to check the patients’ nutritional state; and slow fine motor speed to study the musculoskeletal system.
The results
The study shows that physical frailty appears to be linked to the simultaneous occurrence of multiple impaired system markers, regardless of the specific nature of the markers. The frailty risk for subjects with 1-2 abnormal systems was 4.8 times higher than that of healthy subjects, 11 times higher for people with 3-4 abnormal levels, and 26 times higher for people with 5 or more abnormalities in the biomarkers evaluated.
What’s new
This new concept of frailty in the elderly revolutionizes the previous approach towards this patient population. The physician must concentrate on the global well-being of the patient rather than treat every disease separately. The best medical approach is the one that encompasses as many macro-systems as possible. Moreover, the study confirms that early treatment has a better outcome for the patient than a delayed one.
Study limitations
Even though a significant number of studies corroborate this new notion of frailty, such research consists mostly of pilot studies. Larger and longer studies are necessary to definitively confirm this theory. Furthermore, it remains unclear which subsystem is the specific driver of this multi-systemic dysregulation: the data available seem to identify the metabolic systems as key to this model, but we are currently unable to provide a definitive confirmation.
Moreover, the study will need to be conducted in a population with a specific disease in order to demonstrate that frailty is not merely an indicator of the severity of the disease.
Future outlook
Based on this new knowledge, it will likely be possible to develop a system aimed at evaluating the patient’s frailty risk, in order to address such risk before it leads to an actual medical diagnosis (acute or chronic), thus improving the opportunity for primary and secondary prevention. Moreover, detailed knowledge of the systems involved in physical frailty of the elderly can be used to better distinguish characteristics.
By Alessio Baricich
