Clinical Trials Targeting Aging

Nielsen, Johannes; Bakula, Daniela; Scheibye‐Knudsen, Morten

doi:10.3389/fragi.2022.820215

Cited by 37 publications

(27 citation statements)

References 77 publications

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“…Excessive BA (or biological age acceleration) is associated with all-cause mortality, the prevalence, future incidence, and severity of chronic [9,16,17] and transient diseases, including COVID-19 [15,[18][19][20]. Hence, BA predictors have increasingly gained traction in clinical trials [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Aging clocks, entropy, and the limits of age-reversal

Tarkhov

Denisov

Федичев

2022

Preprint

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We analyze aging signatures in the DNA-methylation and Electronic Medical Records from the UK Biobank datasets and observe that aging is driven by a large number of individually rare and independent transitions between metastable states in a vast configuration space. The compound effect of the configuration changes can be captured by a single stochastic variable, the thermodynamic biological age (tBA), tracking the entropy produced and hence the information lost in the aging process. We show that tBA increases with age, causes the linear aging drift of physiological state variables, reduces resilience, and drives the exponential acceleration of the risks of chronic diseases and death. The entropic character of the aging drift sets limits on possibilities of age-reversal. However, the universal features of configuration transitions suggest practical ways of controlling the rate of aging and thus promising the strongest possible life-extension effects.

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Section: Introductionmentioning

confidence: 99%

Aging clocks, entropy, and the limits of age-reversal

Tarkhov

Denisov

Федичев

2022

Preprint

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“…Rapamycin, as well as its analogue, Sirolimus, was approved by the FDA in 1999 for use as an immunosuppressant. Accordingly, its role in the treatment of cancer has been widely reviewed [ 102 , 103 ], and multiple clinical trials evaluating its efficacy for the treatment of multiple cancers and the development of neurological diseases are ongoing.…”

Section: Clinical Trials Aimed At Delaying the Ageing Processmentioning

confidence: 99%

mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Mota‐Martorell

Jové

Pamplona

2022

IJMS

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Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.

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“…Interestingly, recent cross-species study reported on uterine lavage using human PRP to treat mouse intracavitary uterine synechiae (Kim et al, 2022), where significantly increased STAT3 phosphorylation (a critical transcription factor in tissue regeneration) was observed with upregulated Mt2-mmp, Lox, and Adm, all mediators of tissue remodeling. Cell proliferation, maintenance of genome stability, and metabolic regulation are all influenced by sirtuins (Nielsen et al, 2022), which are nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. Investigators at Huazhong Science & Technology University discovered that SIRT1, SIRT3 and SIRT6 are closely related to ovarian reserve, and may serve as proxy markers of ovarian aging (Zhang et al, 2016).…”

Section: Measuring Menopause and How To Reset Itmentioning

confidence: 99%

Epigenetics, ovarian cell plasticity, and platelet-rich plasma: Mechanistic theories

Sills¹,

Wood

2022

Reproduction and Fertility

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Ovarian platelet-rich plasma (PRP) is claimed to restore fertility potential by improving reserve, an effect perhaps mediated epigenetically by platelet-discharged regulatory elements rather than gonadotropin activated G-protein coupled receptors, as with stimulated in vitro fertilization (IVF). The finding that fresh activated platelet releaseate includes factors able to promote developmental signaling networks necessary to enable cell pluripotency tends to support this theory. The mechanistic uncertainty of intraovarian PRP notwithstanding, at least two other major challenges confront this controversial intervention. First is to clarify how perimenopausal ovarian function is reset to levels consistent with ovulation. Perhaps a less obvious secondary problem is to confine this renewal such that any induced recalibration of cellular plasticity is kept within acceptable physiologic bounds. Thus, any ‘drive’ to ovarian rejuvenation must incorporate both accelerator and brake. Ovarian aging may be best viewed as a safeguard against pathologic overgrowth, where senescence operates as an evolved tumor-suppression response. While most ovary cells reach the close of their metabolic lifespan with low risk for hypertrophy, enhanced lysosomal activity and the pro-inflammatory ‘Senescence Associated Secretory Phenotype’ usually offsets this advantage over time. But is recovery of ovarian fitness possible, even if only briefly prior to IVF? Alterations in gap junctions, bio-conductive features, and modulation of gene regulatory networks after PRP use in other tissues are discussed here alongside early data reported from reproductive medicine.

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Clinical Trials Targeting Aging

Cited by 37 publications

References 77 publications

Aging clocks, entropy, and the limits of age-reversal

Aging clocks, entropy, and the limits of age-reversal

mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Epigenetics, ovarian cell plasticity, and platelet-rich plasma: Mechanistic theories

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