The DOI matches its Crossref record; 119 of the 119 references it cites were found in a registry or an index.
The physical frailty syndrome as a transition from homeostatic symphony to cacophony
Open accessAbstract
Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations. Linda Fried and colleagues argue that physical frailty reflects the dysregulation of a complex dynamical system underpinning health and resilience, and discuss the implications for new prevention and treatment approaches.
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Cites
Frailty in Older Adults: Evidence for a Phenotype
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Self-citationInflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
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Cited by
A complex systems approach to aging biology
Cohen, A. A., Ferrucci, L., Fülöp, T., Gravel, D., Hao, N., Kriete, A., Levine, M. E., Lipsitz, L. A., Olde Rikkert, M. G. M., Rutenberg, A., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00252-6 · Cited by 221
Self-citationPhysical activity guidelines for older people: knowledge gaps and future directions
Izquierdo, M., Duque, G., & Morley, J. E. (2021) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00079-9 · Cited by 214
Wang, B., Wang, L., Gasek, N. S., Zhou, Y., Kim, T., Guo, C., Jellison, E. R., Haynes, L., Yadav, S., Tchkonia, T., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00107-6 · Cited by 145
Diet and exercise in frailty and sarcopenia. Molecular aspects
Millan-Domingo, F., Garcia-Dominguez, E., Gambini, J., Olaso-Gonzalez, G., Viña, J., & Gomez-Cabrera, M. C. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101322 · Cited by 31
Fung, T. T., Rossato, S. L., Chen, Z., Khandpur, N., Rodriguez-Artalejo, F., Willett, W. C., Struijk, E. A., & Lopez-Garcia, E. (2024) · The American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.05.006 · Cited by 24
Metadata
- Authors
- Fried, L. P., Cohen, A. A., Xue, Q.-L., Walston, J., Bandeen-Roche, K., & Varadhan, R.
- Venue
- Nature Aging
- Published
- 2021-01-14
- Volume
- 1
- Issue
- 1
- Pages
- 36-46
- ISSN
- 2662-8465 (ISSN-L)
- OpenAlex
- W3119134848
- Cited by
- 584
- References
- 119
- FWCI
- 42.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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