Oxidative stress, genomic features and DNA repair in frail elderly: A systematic review

Abstract

Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality, morbidity, disability, hospitalization, and institutionalization. Although it is generally recognized to have a biological basis, no particular biological trait has been consistently associated to frailty status so far. In this work, epidemiological studies evaluating association of frailty status with alterations at cellular level - namely oxidative stress, genomic instability and DNA damage and repair biomarkers -were revised and compared. A total of 25 studies fulfilled inclusion/exclusion criteria and, consequently, were included in the review. Variations of oxidative stress biomarkers were often associated to frailty status in older people. On the contrary, genomic instability seems not to be linked to frailty. The only study which addressed the possible relationship between DNA repair modulations and frailty status also failed in finding association. Despite the large number of cellular alterations known to be associated with frailty, studies on this issue are still very scarce and limited to some of the possible cellular targets. The established link between DNA repair, genomic instability, and age and age-related disorders, encourage deeper investigations on this line.

Assessing onset, prevalence and survival in mice using a frailty phenotype

“…The increased prevalence of frailty with aging likely represents decreased resilience to ongoing stress, which ultimately could lead to extensive cellular alterations. Some of these alterations include genomic instability, mutations, altered gene expression, loss of cell division potential, cell death and/or impaired intercellular communication [22]. Hence, identifying the onset and prevalence of frailty across the lifespan, in addition to predicting mortality, has the potential to yield information about susceptibility and resilience to the aging processes.…”

<p>Assessment of the relationship between frailty syndrome and the nutritional status of older patients</p>

“…There are several instruments to screen the risk of frailty syndrome. The assessments include physical criteria, neurological assessment, psychological symptoms and laboratory test outcomes 6. Well-known instruments to identify frailty are based on the phenotypic model by Fried et al or the deficit accumulation model.…”

Exploring Genetic Outcomes as Frailty Biomarkers

“…In this regard, frailty is commonly accepted to have a strong biological component resulting from cumulative cellular damage over the life course (9), although other aspects of aging involving intercellular communication, breakdown of homeostasis at the organism level, and so on probably participate in frailty development. Increased levels of damage can lead to different cellular alterations, including genomic instability, mutations, altered gene expression, loss of cell division potential, cell death, or impaired intercellular communication, among others (10). These alterations at the cellular and molecular levels could be a good basis to establish frailty biomarkers.…”