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

Area of Science:

• Gerontology
• Developmental Biology
• Public Health

Background:

• Frailty is a significant target for interventions to extend healthy lifespan.
• The timing of frailty predisposition during the life course remains an open question.
• The developmental origins of health and disease (DOHaD) theory links fetal environment to adult lifestyle-related disorders.

Purpose of the Study:

• To propose that frailty has a fetal origin, aligning with the DOHaD spectrum.
• To explore the relationship between fetal programming, frailty, and age-related diseases like sarcopenia and dementia.
• To advocate for a "total" life-course strategy to combat frailty.

Main Methods:

• Literature review exploring the link between intrauterine growth restriction and frailty-related disorders.
• Analysis of current frailty research focusing on vascular and metabolic alterations.
• Conceptual framework integrating DOHaD principles with frailty etiology.

Main Results:

• Evidence suggests a potential link between fetal programming and the development of frailty.
• Vascular dysfunction and metabolic alterations are implicated in both lifestyle-related disorders and frailty.
• Intrauterine growth restriction is highlighted as a key factor in exploring frailty's origins.

Conclusions:

• Frailty may have its origins in the fetal environment, representing a DOHaD spectrum condition.
• A comprehensive "total" life-course approach is necessary to effectively combat frailty.
• Interdisciplinary collaboration among obstetricians, pediatricians, physicians, and gerontologists is crucial for addressing age-related diseases.