Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review

Abstract

The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8CD28T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.

Mastication and oral sensory function in frail edentulous elderly: a case–control study

“…This finding is in agreement with some reports, which revealed greater bite force in healthy patients than in those with the FP. Elderly people with the FP probably have reduced MBF as a result of the multisystem physiological changes related to frailty. Therefore, reductions of strength‐related hormonal factors, such as testosterone, insulin‐like growth factor‐I and interleukin‐6, associated with immune dysfunction and oxidative stress, are possibly related to the decline in muscle strength.…”

Can We Distinguish Age-Related Frailty from Frailty Related to Diseases? Data from the MAPT Study

“…Several biological mechanisms have been suggested for the pathogenesis of frailty, such as inflammation, endocrinological and genetic changes (28). However, to the best of our knowledge, in the context of frailty there are no biomarkers able to differentiate the changes related to aging and those related to diseases (28)(29) (30). Moreover, geroscience could help define the concept of age-related frailty, and to establish the main processes leading to frailty in the absence of evolving chronic diseases and intervening medical events.…”

Resilience in gerontology and geriatrics (review)

“…Известно, что ряд ключевых генов, например, SLC6A4, COMT, BDNF, FKB5 и прочие ассоциированы с формированием возрастной жизнеспособности. Так, ген SLC6A4 обусловливает экспрессию рецепторов к серотонину, что обусловливает формирование благоприятного типа старения за счет более высокой возрастной жизнеспособности [28].…”

“…При снижении активности мозгового нейротрофического фактора BDNF имеет место нарушение качества межнейронных связей, что сопровождается развитием когнитивного дефицита и снижением уровня адаптации центральной нервной системы к стрессовым воздействиям. Значительную роль в формировании должного уровня возрастной жизнеспособности играют системы серотонина, адреналина и норадреналина, дофамина [29,30].…”