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. 2024 Mar 12:8:21-50.
doi: 10.15698/cst2024.03.294. eCollection 2024.

The missing hallmark of health: psychosocial adaptation

Carlos López-Otín  1   2   3 , Guido Kroemer  1   4   5
Affiliations

The missing hallmark of health: psychosocial adaptation

Carlos López-Otín et al. Cell Stress. .

Abstract

The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features of spatial compartmentalization (integrity of barriers, containment of local perturbations), maintenance of homeostasis over time (recycling & turnover, integration of circuitries, rhythmic oscillations) and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, repair & regeneration). These hallmarks affect all eight somatic strata of the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries and meta-organism). Here we postulate that mental and socioeconomic factors must be added to this 8×8 matrix as an additional hallmark of health ("psychosocial adaptation") and as an additional stratum ("psychosocial interactions"), hence building a 9×9 matrix. Potentially, perturbation of each of the somatic hallmarks and strata affects psychosocial factors and vice versa. Finally, we discuss the (patho)physiological bases of these interactions and their implications for mental health improvement.

Keywords: aging; mental health; psychiatry; psychology.

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Conflict of interest statement

Conflict of Interest: G.K. has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. G.K. is in the scientific advisory boards of Hevolution, Institut Servier and Longevity Vision Funds. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. G.K.'s wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9 m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. G.K.'s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim.

Figures

Figure 1
Figure 1. FIGURE 1: The psychosocial adaptation as a new hallmark of health.
The scheme represents the links between psychosocial adaptation and the eight previously proposed hallmarks of health: integrity of barriers, containment of local perturbations, recycling & turnover, integration of circuitries, rhythmic oscillations, homeostatic resilience, hormetic regulation, and repair & regeneration. These hallmarks are grouped into three categories: spatial compartmentalization, maintenance of homeostasis over time, and adequate responses to stress.
Figure 2
Figure 2. FIGURE 2: Square matrix representing the relationships between health hallmarks and body strata.
The 9×9 matrix depicts the bidirectional connections between the nine hallmarks of health and the nine organizational strata of the human body. The relationships between psychosocial adaptation and psychosocial interactions are specifically enhanced.
Figure 3
Figure 3. FIGURE 3: Mouse models of psychosocial stress and response pathways resulting in psychosocial adaptation.
(A) Prototypic models of psychosocial stress in mice include chronic social defeat and dominance tube test models, as well as models of acute stress such as tube restrains, cage switching and short-term social isolation. (B) Different stressors including psychosocial stress promote a compendium of physiological and behavioral alterations coupled to activation of the sympathetic-adrenal medullary (SAM) and the hypothalamic pituitary adrenal (HPA) axes, as well as additional pathways which need to be further characterized. Deconvoluting the molecular pathways linking social stress to compromised mental and physical health may lead to the introduction of intervention strategies for improving psychosocial adaptation to stress.
Figure 4
Figure 4. FIGURE 4: Psychosocial dimension of health hallmarks implicated in spatial compartmentalization.
Links between psychosocial adaptation and the mechanisms responsible for the integrity of biological barriers and the containment of local perturbations.
Figure 5
Figure 5. FIGURE 5: Psychosocial dimension of the hallmarks of health involved in maintenance of homeostasis.
Interconnectivity between psychosocial adaptation and mechanisms of recycling and turnover in tissues and cells, crosstalk among different circuitries (cell-tissue-organ-system), and their synchronization with circadian, infradian or ultradian rhythmic oscillations.
Figure 6
Figure 6. FIGURE 6: Psychosocial dimension of the hallmarks of health involved in responses to stress.
Interactions between psychosocial adaptation and mechanisms of homeostatic resilience, hormetic regulation and repair and regeneration strategies aimed at achieving biological stability and maintenance of health, including mental health.
Figure 7
Figure 7. FIGURE 7: Psychosocially relevant perturbations across health hallmarks and body strata.
The nine hallmarks of health integrate and leverage the multifunctionality of each hierarchical stratum and orchestrate the complex interactions across the nine body strata encompassing the distinct molecular, organellar, cellular, supracellular, tissular, systemic, organismal, meta-organismal and psychosocial components. Examples of specific psychosocial dysfunctions or disorders affecting the nine different hallmarks and strata are shown to illustrate the multidimensional basis of health, including mental health.
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    Montégut L, López-Otín C, Kroemer G. Montégut L, et al. Mol Cancer. 2024 May 18;23(1):106. doi: 10.1186/s12943-024-02020-z. Mol Cancer. 2024. PMID: 38760832 Free PMC article. Review.

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