Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan

Kaur, Prameet; Otgonbaatar, Agimaa; Ramamoorthy, Anupriya; Chua, Ellora Hui Zhen; Harmston, Nathan; Gruber, Jan; Tolwinski, Nicholas S.

doi:10.18632/aging.204347

Cited by 7 publications

(2 citation statements)

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“…The relationship between stem cell exhaustion and cellular senescence is complex, may be mediated by many factors and is not completely known (reviewed in [ 76 ]). Besides a simple implication that cellular senescence contributes to stem cell exhaustion, both phenomena likely interplay to drive the process of aging [ 77 ]. Senescent cells develop the senescence-associated secretory phenotype (SASP) featured by the overproduction of growth factors, proteases, pro-inflammatory cytokines and extracellular vesicles, which may act in autocrine or paracrine manner [ 78 ].…”

Section: Stem Cell Exhaustion and Cellular Senescencementioning

confidence: 99%

Different Aspects of Aging in Migraine

Fila¹,

Pawłowska²,

Szczepańska³

et al. 2023

Aging and disease

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Migraine is a common neurological disease displaying an unusual dependence on age. For most patients, the peak intensity of migraine headaches occurs in 20s and lasts until 40s, but then headache attacks become less intense, occur less frequently and the disease is more responsive to therapy. This relationship is valid in both females and males, although the prevalence of migraine in the former is 2-4 times greater than the latter. Recent concepts present migraine not only as a pathological event, but rather as a part of evolutionary adaptive response to protect organism against consequences of stress-induced brain energy deficit. However, these concepts do not fully explain that unusual dependence of migraine prevalence on age. Many aspects of aging, both molecular/cellular and social/cognitive, are interwound in migraine pathogenesis, but they neither explain why only some persons are affected by migraine, nor suggest any causal relationship. In this narrative/hypothesis review we present information on associations of migraine with chronological aging, brain aging, cellular senescence, stem cell exhaustion as well as social, cognitive, epigenetic, and metabolic aging. We also underline the role of oxidative stress in these associations. We hypothesize that migraine affects only individuals who have inborn, genetic/epigenetic, or acquired (traumas, shocks or complexes) migraine predispositions. These predispositions weakly depend on age and affected individuals are more prone to migraine triggers than others. Although the triggers can be related to many aspects of aging, social aging may play a particularly important role as the prevalence of its associated stress has a similar age-dependence as the prevalence of migraine. Moreover, social aging was shown to be associated with oxidative stress, important in many aspects of aging. In perspective, molecular mechanisms underlying social aging should be further explored and related to migraine with a closer association with migraine predisposition and difference in prevalence by sex.

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Section: Stem Cell Exhaustion and Cellular Senescencementioning

confidence: 99%

Different Aspects of Aging in Migraine

Fila¹,

Pawłowska²,

Szczepańska³

et al. 2023

Aging and disease

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“…There is a lot of experimental data pointing out that such installation could happen under the influence of so-called Yamanaka factors (e.g. [88,89]), and corresponding interventions may have high rejuvenating potential [90][91][92][93].…”

Section: Model Development and Preliminary Validationmentioning

confidence: 99%

Cell Level- Modeling of Aging and Rejuvenation

Koptyug,

Sukhovei,

Kostolomova

et al. 2023

OBM Geriatr

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Understanding processes related to human aging and rejuvenation relies on experimental data and advanced models operating at different levels. There are several existing conceptual and specific modeling approaches. However, one of the existing tasks is compiling generic models linking properties at cell and cell-element levels to properties at systemic levels - tissue, organ, and whole body. One of the critical issues in the relevant models is the enormity of interacting components at the cell and sub-cell levels needed to represent the properties of high-level systems properly. This paper describes a promising approach to modeling and simulation at the cell population level for studying aging and rejuvenation. It also presents initial conclusions formulated based on the results of modeling and experiments coupled to it. The model is based on the concepts of the proliferation niche and homeostatic cell number stabilization in the cell population through the associated action of proliferation and apoptosis. Importantly, we address the issue of defining “aging” and “rejuvenation” for cell populations containing large numbers of cells of different ages. It is possible to demonstrate that homeostatic regulation can be performed by maintaining the concentration of a single regulatory substance. Predictions and simulations of the proposed model are compared to data from existing publications and experiments specifically conducted to validate the model. Currently, none of the available data contradicts the modeling results at the proposed level of detail. However, an inadequate number of elements and the employed statistical approach further limit progress in such modeling. Expanding the proposed method to include a realistic number of features representing human tissues, organs, and body and to allow for proper modeling of aging and rejuvenation processes requires more advanced modeling techniques.

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