Perspectives on frailty as a total life‐course disease with consideration of the fetal environment

Abstract

Frailty attracts research as it represents a significant target for intervention to extend the healthy life span. An unanswered question in this field is the time point during the life-course at which an individual becomes predisposed to frailty. Here, we propose that frailty has a fetal origin and should be regarded as part of the spectrum of the developmental origins of health and disease. The developmental origins of health and disease theory originated from findings linking the fetal environment to lifestyle-related disorders such as hypertension and diabetes. Coincidentally, a recent trend in frailty research also centers on vascular dysfunction and metabolic alterations as the causality of lifestyle-related disorders such as sarcopenia and dementia. Here, we explore the relationship between fetal programming, frailty-related disorders (sarcopenia and dementia), and other age-related diseases mainly based on reports on intrauterine growth restriction. We propose a "total" life-course approach to combat frailty. With this viewpoint, not only physicians and gerontologists but also obstetricians and pediatricians should team up to overcome age-related diseases in the elderly.

Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty

“…Growing evidence has shown that lower birth weight is a critical determinant of long-term health outcomes (5,24). The MR results of the study confirmed that lower birth weight was causally associated with an increased risk of frailty, which was consistent with the findings from previous observational studies.…”