Physiological Systems in Promoting Frailty

Laís R. Perazza

doi:10.1002/cphy.c210034

2022-04-26

Laís R. Perazza

Holly M. Brown‐Borg

LaDora V. Thompson *

DOI：10.1002/cphy.c210034

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摘要

En 中文

Frailty is a complex syndrome affecting a growing sector of the global population as medical developments have advanced human mortality rates across the world. Our current understanding of frailty is derived from studies conducted in the laboratory as well as the clinic, which have gen-erated largely phenotypic information. Far fewer studies have uncovered biological underpinnings driving the onset and progression of frailty, but the stage is set to advance the field with preclinical and clinical assessment tools, multiomics approaches together with physiological and biochemical methodologies. In this article, we provide comprehensive coverage of topics regarding frailty assessment, preclinical models, interventions, and challenges as well as clinical frameworks and prevalence. We also identify central biological mechanisms that may be at play including mito-chondrial dysfunction, epigenetic alterations, and oxidative stress that in turn, affect metabolism, stress responses, and endocrine and neuromuscular systems. We review the role of metabolic syndrome, insulin resistance and visceral obesity, focusing on glucose homeostasis, adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and nicotinamide adenine dinucleotide (NAD+) as critical players influencing the age-related loss of health. We further focus on how immunometabolic dysfunction associates with oxidative stress in promoting sarcopenia, a key contributor to slowness, weakness, and fatigue. We explore the bio-logical mechanisms involved in stem cell exhaustion that affect regeneration and may contribute to the frailty-associated decline in resilience and adaptation to stress. Together, an overview of the interplay of aging biology with genetic, lifestyle, and environmental factors that contribute to frailty, as well as potential therapeutic targets to lower risk and slow the progression of ongoing disease is covered.

Keyword:

MESENCHYMAL STEM-CELLS

GROWTH-FACTOR-I

MUSCLE MITOCHONDRIAL-FUNCTION

RANDOMIZED CONTROLLED-TRIAL

MULTIPLE CHRONIC CONDITIONS

CU/ZN SUPEROXIDE-DISMUTASE

ALL-CAUSE MORTALITY

AGE-RELATED-CHANGES

CHAIN AMINO-ACIDS

EXTENDS LIFE-SPAN