PMID- 35578945
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20230721
IS  - 2040-4603 (Electronic)
IS  - 2040-4603 (Linking)
VI  - 12
IP  - 3
DP  - 2022 Apr 26
TI  - Physiological Systems in Promoting Frailty.
PG  - 3575-3620
LID - 10.1002/cphy.c210034 [doi]
AB  - 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 generated 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 mitochondrial 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 
      biological 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. (c) 2022 American Physiological Society. Compr Physiol 12:1-46, 
      2022.
CI  - Copyright (c) 2022 American Physiological Society. All rights reserved.
FAU - Perazza, Lais R
AU  - Perazza LR
AD  - Department of Physical Therapy and Athletic Training, Boston University, Boston, 
      Massachusetts, USA.
FAU - Brown-Borg, Holly M
AU  - Brown-Borg HM
AD  - Department of Biomedical Sciences, University of North Dakota, Grand Forks, North 
      Dakota, USA.
FAU - Thompson, LaDora V
AU  - Thompson LV
AD  - Department of Physical Therapy and Athletic Training, Boston University, Boston, 
      Massachusetts, USA.
LA  - eng
GR  - K07 AG072124/AG/NIA NIH HHS/United States
GR  - R56 AG067724/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220426
PL  - United States
TA  - Compr Physiol
JT  - Comprehensive Physiology
JID - 101574442
SB  - IM
MH  - Aging/physiology
MH  - *Frailty
MH  - Humans
MH  - *Insulin Resistance
MH  - Oxidative Stress
MH  - United States
PMC - PMC9531553
MID - NIHMS1839399
EDAT- 2022/05/18 06:00
MHDA- 2022/05/20 06:00
PMCR- 2022/10/04
CRDT- 2022/05/17 04:13
PHST- 2022/05/17 04:13 [entrez]
PHST- 2022/05/18 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2022/10/04 00:00 [pmc-release]
AID - 10.1002/cphy.c210034 [doi]
PST - epublish
SO  - Compr Physiol. 2022 Apr 26;12(3):3575-3620. doi: 10.1002/cphy.c210034.