To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty

Abstract

Many factors have contributed to rendering frailty an emerging, relevant, and very popular concept. First, many pandemics that have affected humanity in history, including COVID-19, most recently, have had more severe effects on frail people compared to non-frail ones. Second, the increase in human life expectancy observed in many developed countries, including Italy has led to a rise in the percentage of the older population that is more likely to be frail, which is why frailty is much a more common concern among geriatricians compared to other the various health-care professionals. Third, the stratification of people according to the occurrence and the degree of frailty allows healthcare decision makers to adequately plan for the allocation of available human professional and economic resources. Since frailty is considered to be fully preventable, there are relevant consequences in terms of potential benefits both in terms of the clinical outcome and healthcare costs. Frailty is becoming a popular, pervasive, and almost omnipresent concept in many different contexts, including clinical medicine, physical health, lifestyle behavior, mental health, health policy, and socio-economic planning sciences. The emergence of the new "science of frailty" has been recently acknowledged. However, there is still debate on the exact definition of frailty, the pathogenic mechanisms involved, the most appropriate method to assess frailty, and consequently, who should be considered frail. This narrative review aims to analyze frailty from many different aspects and points of view, with a special focus on the proposed pathogenic mechanisms, the various factors that have been considered in the assessment of frailty, and the emerging role of biomarkers in the early recognition of frailty, particularly on the role of mitochondria. According to the extensive literature on this topic, it is clear that frailty is a very complex syndrome, involving many different domains and affecting multiple physiological systems. Therefore, its management should be directed towards a comprehensive and multifaceted holistic approach and a personalized intervention strategy to slow down its progression or even to completely reverse the course of this condition.

Keywords: aging; epidemics/pandemics; frailty; frailty assessment; frailty pathogenesis; interventions; mitochondrial dysfunction; risk factors.

Figure 1

The number of papers published in the literature citing the term “frailty” and published since the year 1950 are reported for the indicated years. Data were obtained from Pubmed, the National Library of Medicine, and the U.S. Department of Health and Human Services (HHS), available at https://pubmed.ncbi.nlm.nih.gov (accessed on 2 November 2023).

Figure 2

The complex network of frailty involving different domains. The different factors that influence frailty are reported.

Figure 3

The Great Wave off the Coast of Kanagawa. Katsushika Hokusai, Japan 1831 [33].

Figure 4

The central role of mitochondria in aging.

Figure 5

Risk factors for COVID-19 mortality. Adapted from [234]. gray circle, reference group; blue circle, 1 morbidity; green circle, 2 morbidities; yellow circle, 3 morbidities; orange circle, 4 morbidities; red circle, 5 morbidities.

Figure 6

Physical frailty based on the Fried phenotype model. Adapted from Fried et al. [9].