Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

Published: April 10, 2024

Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity vitamin D metformin, appear significantly reduce all-cause mortality prolong life expectancy. This should be confirmed by interventional studies. cell family is the most advanced trial development [phase 2b randomized controlled (RCT)]. An allogeneic bone marrow preparation (Lomecel-B) reduced locomotor frailty older people. improvement locomotion was modest. In future, attempts could made improve potency through a precondition genetic modification naive cells. Autologous adipose cell-assisted fat grafting increased graft survival, facial volume, skin quality. association senolytic drugs dasatinib quercetin well tolerated, with low brain penetration undetectable levels quercetin. sirtuin-1 activator resveratrol (combined physical exercise) improved function adults limitations. NAD+ precursor riboside exercise performance. conclusion, Lomecel-B agent for (phase frailty), followed riboside.

Language: Английский

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The gerontological saga of antidiabetic biguanides: From ignorance to prudence via high hopes

Translational Medicine of Aging, Journal Year: 2024, Volume and Issue: 8, P. 12 - 19

Published: Jan. 1, 2024

The history of the discoveries that shaped current attitudes to use antidiabetic biguanides, mainly metformin, as antiaging agents is reviewed. An emphasis made on mounting evidence diseases aging including type II diabetes mellitus, metabolic syndrome, neurodegenerative conditions and cancer are featured in clinical trials metformin increasingly recognized those for which physical exercises effective risk reduction therapy enhancement. known primary molecular targets map some signaling pathways by effects two most robust physiological interventions, i.e. energy consumption increase calorie intake restriction, transduced cellular systems implicated regulating balance between, one hand, growth proliferation and, other maintenance repair. However, allegedly can reproduce but partly biased ways interventions. In particular, although may help maintain conditions, it hampers gains fitness afforded exercises. These observations should be taken into account advising healthy people engaged increasing their or patients whose muscular mass decreased during disease restored thereafter.

Language: Английский

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Sirtuins and the Twelve Hallmarks of Ageing: A Framework for Understanding Ageing Processes and Targeted Intervention

International Journal of Innovative Science and Research Technology (IJISRT), Journal Year: 2024, Volume and Issue: unknown, P. 3230 - 3245

Published: June 18, 2024

Ageing is an innate phenomenon that has not been fully elucidated, despite increasing research on ageing in response to the worsening global population. This demographic shift leads profound ethical and social implications for human health, delineated by twelve hallmarks of ageing. Sirtuins, a family NAD+ - dependent enzymes, are key process, thus have more extensively studied recent years. review summarises mechanisms molecular pathways through which sirtuins modulate each hallmark therefore influence incidence age-related illnesses. The mounting evidence close interaction between longevity indicates sirtuins’ function as therapeutic targets extending health span life span. We further summarise interventions target changes molecular, cellular, systemic levels.

Language: Английский

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Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: July 2, 2024

Abstract Background Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though precise mechanisms remain largely unknown. This study aimed investigate impact polygenic scores (PRS) WM integrity, together DNA methylation, gene expression on aging in cross-sectional healthy cohort. The PRSs were calculated using genome-wide association (GWAS) summary statistics magnetic resonance imaging (MRI) markers including hyperintensities, fractional anisotropy (FA), mean diffusivity (MD). These utilized predict changes evaluate their correlation structural brain changes, which distinguish individuals higher lower scores. To reduce dimensionality data identify methylation transcriptomic Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, canonical algorithm used integrate three types omics (PRS, data) an individual “omics” signature that distinguishes subjects varying profiles. Results We found positive between MD-PRS long-term memory, as well effectively discriminating memory Furthermore, we observed enrichment signals genes related both vascular non-vascular factors. Age-related alterations indicated dysregulation critical molecular features signaling pathways involved lifespan regulation. integration multi-omics underscored involvement synaptic dysfunction, axonal degeneration, microtubule organization, glycosylation process aging. Conclusions findings provide valuable insights into biological underlying coherence Additionally, they highlight how age-associated contribute

Language: Английский

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Telomere Reprogramming and Cellular Metabolism: Is There a Link?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10500 - 10500

Published: Sept. 29, 2024

Telomeres—special DNA–protein structures at the ends of linear eukaryotic chromosomes—define proliferation potential cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with increased proliferative specific types, such as stem germ This can be permanent in these activated temporally during immune activation regeneration processes. The lengthening mechanisms coupled cells’ need for energy building resources. To obtain necessary nutrients, are capable finely regulating production consumption, switching between catabolic anabolic In this review, we focused on interconnection metabolism programs programmed proliferation, maturation, early embryonic development, neoplastic lesion growth, activation. It generally accepted disturbance influences biological processes promotes dysfunctionality. Here, propose metabolic conditions within proliferating should involved mechanisms, length serve marker defects cellular functionality. We it possible reprogram order regulate activity cells, which important development approaches regeneration, modulation, cancer therapy. further investigations area improve understanding manipulation molecular regulation metabolism, aging.

Language: Английский

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