Is anti-ageing drug discovery becoming a reality?

Moskalev, Alexey

doi:10.1080/17460441.2020.1702965

Cited by 16 publications

(5 citation statements)

References 33 publications

(35 reference statements)

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“…Several pharmacologic approaches have been reported to delay age‐related manifestations including reversal of stem cell dysfunction and extension of lifespan (Moskalev, 2020 ; Partridge et al, 2020 ). Although none are yet approved for ameliorating the effects of aging in humans, metformin and rapamycin have been studied as regulators of cellular metabolic activities that are linked to aging phenotypes (An et al, 2020 ; Blagosklonny, 2019 ; Moskalev et al, 2022 ; Novelle et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Intestinal stem cell aging at single‐cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics

et al. 2023

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The intestinal epithelium consists of cells derived from continuously cycling Lgr5hi intestinal stem cells (Lgr5hi ISCs) that mature developmentally in an ordered fashion as the cells progress along the crypt‐luminal axis. Perturbed function of Lgr5hi ISCs with aging is documented, but the consequent impact on overall mucosal homeostasis has not been defined. Using single‐cell RNA sequencing, the progressive maturation of progeny was dissected in the mouse intestine, which revealed that transcriptional reprogramming with aging in Lgr5hi ISCs retarded the maturation of cells in their progression along the crypt‐luminal axis. Importantly, treatment with metformin or rapamycin at a late stage of mouse lifespan reversed the effects of aging on the function of Lgr5hi ISCs and subsequent maturation of progenitors. The effects of metformin and rapamycin overlapped in reversing changes of transcriptional profiles but were also complementary, with metformin more efficient than rapamycin in correcting the developmental trajectory. Therefore, our data identify novel effects of aging on stem cells and the maturation of their daughter cells contributing to the decline of epithelial regeneration and the correction by geroprotectors.

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Section: Introductionmentioning

confidence: 99%

Intestinal stem cell aging at single‐cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics

et al. 2023

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“…Based on the present level of knowledge, the geroprotective therapies targeting the mechanisms of immunosenescence are just emerging [85]. Their studies need to intensify, with a broader identification of potential clinically applicable interventions and biomarkers, and their extensive pre-clinical and clinical testing [85].…”

mentioning

confidence: 99%

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

Moskalev¹,

Stambler²,

Caruso³

2020

Aging and disease

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The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article.

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“…Anti-ageing drugs, also known as geroprotectors, are pharmacological agents that decrease the rate of ageing and extend lifespan [184]. Although anti-ageing treatments have been shown to extend the lifespan of model organisms, there are still no clinically proven human geroprotectors.…”

Section: Current Anti-ageing Therapies and Challengesmentioning

confidence: 99%

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

Stevanović

Lazic

Schwirtlich

et al. 2023

IJMS

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The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.

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Is anti-ageing drug discovery becoming a reality?

Cited by 16 publications

References 33 publications

Intestinal stem cell aging at single‐cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics

Intestinal stem cell aging at single‐cell resolution: Transcriptional perturbations alter cell developmental trajectory reversed by gerotherapeutics

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

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