The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 816 - 816

Published: Feb. 10, 2025

Aging represents a complex biological phenomenon marked by the progressive deterioration of physiological functions over time, reduced resilience, and increased vulnerability to age-related diseases, ultimately culminating in mortality. Recent research has uncovered diverse molecular mechanisms through which metformin extends its benefits beyond glycemic control, presenting it as promising intervention against aging. This review delves into anti-aging properties metformin, highlighting role mitochondrial energy modulation, activation AMPK-mTOR signaling pathway, stimulation autophagy, mitigation inflammation linked cellular Furthermore, we discuss influence on epigenetic modifications that underpin genomic stability homeostasis. Metformin's potential addressing age-associated disorders including metabolic, cardiovascular, neurodegenerative diseases is also explored. The Targeting with Metformin (TAME) trial aims provide key evidence efficacy delaying aging humans. Despite these insights, significant challenges persist gaining more comprehensive understanding underlying mechanisms, determining optimal dosing strategies, evaluating long-term safety non-diabetic populations. Addressing crucial fully realizing metformin's an therapeutic.

Language: Английский

Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13144 - 13144

Published: Dec. 6, 2024

The efficacy of assisted reproductive technologies (ARTs) in older women remains constrained, largely due to an incomplete understanding the underlying pathophysiology. This review aims consolidate current knowledge on age-associated mitochondrial alterations and their implications for ovarian aging, with emphasis causes DNA (mtDNA) mutations, repair mechanisms, future therapeutic directions. Relevant articles published up 30 September 2024 were identified through a systematic search electronic databases. free radical theory proposes that reactive oxygen species (ROS) inflict damage mtDNA impair function essential ATP generation oocytes. Oocytes face prolonged pressure persisting five decades. MtDNA exhibits limited capacity double-strand break repair, heavily depending poly ADP-ribose polymerase 1 (PARP1)-mediated single-strand breaks. process depletes nicotinamide adenine dinucleotide (NAD⁺) ATP, creating detrimental cycle where continued further compromises oocyte functionality. Interventions interrupt this destructive may offer preventive benefits. In conclusion, cumulative burden mutations demands can lead depletion elevate risk aneuploidy, ultimately contributing ART failure women.

Language: Английский