The stress of aging
Abstract
Although the evolutionary theories of aging are quite well established, our knowledge about how we age is still very limited. The abundance and heterogeneity of available mechanistic theories of aging implicitly suggest that this phenomenon is overly complex and unlikely to be explained by a single pathway. Moreover, although aging remains a unique process, it is characterized by heterogeneous manifestations, not only determining inter-individual variations, but even intra-individual diversities. Such heterogeneity renders the inner nature of the aging process of difficult evaluation in older persons due to the potential biases introduced by multiple age-related social, biological, and clinical factors (and responsible for the evidence-based issue in geriatrics). Moving from the difficulties in translating anti-aging preclinical interventions into clinical trials, an alternative approach is illustrated. We encourage moving to a holistic evaluation of aging by adopting specific and consequent modifications in the design and conduction of clinical research. Such approach is today commonly applied in the clinical setting where the complexity of older patients often requires multidimensional interventions to adequately target the geriatric syndromes. Consistently, interventions targeting the aging process may result ineffective if too focused on a single underlying causal mechanism and/or failing to capture the complexity of the phenomenon. In this context, frailty (a geriatric syndrome characterized by age-related declines occurring across multiple physiologic systems) may indeed represent a clinically relevant threshold throughout the continuum of the aging process and a promising benchmark to test multidomain interventions against age-related conditions.
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The combined results of short-term metabolic studies comparing protein synthesis and breakdown between younger and older adults are inconclusive and sometimes contradictory for the fasted state.
“Given the complex nature of the aging process, 48 it is not surprising that the combined results of these studies are inconclusive, and sometimes contradictory, for the fasted state.”
From Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group (2013) · cites this paper as [48]
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Self-citationRetractedTHE EUROPEAN UNION GERIATRIC MEDICINE SOCIETY (EUGMS) WORKING GROUP ON FRAILTY IN OLDER PERSONS
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Muller’s ratchet as a mechanism of frailty and multimorbidityPreprint
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Füzéki, E., & Banzer, W. E. (2018) · Springer Reference Pflege, Therapie, Gesundheit · doi:10.1007/978-3-662-54179-1_32-1
Füzéki, E., & Banzer, W. E. (2021) · Springer Reference Pflege, Therapie, Gesundheit · doi:10.1007/978-3-662-54179-1_32-2
Füzéki, E., & Banzer, W. E. (2022) · Springer Reference Pflege, Therapie, Gesundheit · doi:10.1007/978-3-662-65219-0_32
Tiwari, S., Tyagi, A., Tiwari, S., Milan, A., Kumar, D., & Kant, C. (2025) · Environment Conservation Journal · doi:10.36953/ecj.34092025
Ortega-Hernández, E., Addor, G., Bhatia, S., Lewinsohn, M., & Sottas, P. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1732426
- Authors
- Cesari, M., Vellas, B., & Gambassi, G.
- Affiliations
- Inserm (FR)
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Cesari, Matteo
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 48
- Issue
- 4
- Pages
- 451-456
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2048552357
- Cited by
- 83
- References
- 58
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 8 · 2014: 8 · 2013: 7
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- aging, frailty, geriatric syndromes, multidomain intervention, anti-aging interventions
- MeSH terms
- Adaptation, Physiological, Aged, Aging, Geriatrics, Humans, Patient Care Team, Social Adjustment, Stress, Physiological, Systems Theory, Frail Elderly, Evidence-Based Medicine, Biomedical Research
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