Journal of Cell Biology and Metabolism

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Rapid Communication - Journal of Cell Biology and Metabolism (2025) Volume 7, Issue 2

Role of Sirtuins in Cellular Aging and Metabolic Health

Yin Walter*

Department of science, Durham University, South Road, Durham, UK.

*Corresponding Author:
Yin Walter
Department of science, Durham University
South Road, Durham, UK
E-mail: Water@durham.ac.uk

Received: 03-Apr-2025, Manuscript No. AACBM-25-164644; Editor assigned: 04-Apr-2025, PreQC No. AACBM-25-1646445(PQ); Reviewed: 18-Apr-2025, QC No AACBM-25-1646445; Revised: 21-Apr-2025, Manuscript No. AACBM-25-1646445(R); Published: 28-Apr-2025, DOI:10.35841/aacbm-7.2.265

Citation: Walter Y. Role of sirtuins in cellular aging and metabolic health. J Cell Biol Metab. 2025;7(2):265.

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Introduction

Sirtuins are a family of NAD⁺-dependent enzymes that play critical roles in regulating cellular homeostasis, aging, and metabolism. Originally discovered in yeast as lifespan-extending factors, sirtuins have since been identified in various organisms, including mammals, where they influence diverse biological processes. There are seven known mammalian sirtuins (SIRT1–SIRT7), each with distinct subcellular localizations and functions, ranging from gene expression and DNA repair to mitochondrial function and stress resistance. Their activity is closely linked to cellular energy status, making them key mediators of metabolic health and aging [1, 2].

Sirtuins act primarily through deacetylation or ADP-ribosylation of target proteins, modifying their activity and stability. SIRT1, the most extensively studied member, is located in the nucleus and cytoplasm and influences transcription factors such as PGC-1α, FOXO, and NF-κB. Through these interactions, SIRT1 regulates mitochondrial biogenesis, antioxidant defense, inflammation, and glucose and lipid metabolism. SIRT1 activation enhances insulin sensitivity, promotes fatty acid oxidation, and reduces inflammatory signaling, linking it directly to protection against metabolic disorders like obesity and type 2 diabetes [3, 4].

Mitochondrial sirtuins, particularly SIRT3, SIRT4, and SIRT5, play pivotal roles in maintaining mitochondrial integrity and function. SIRT3 deacetylates key enzymes involved in the tricarboxylic acid (TCA) cycle, fatty acid oxidation, and the electron transport chain, thereby optimizing mitochondrial metabolism and reducing reactive oxygen species (ROS) production. SIRT3 also supports cellular resistance to oxidative stress, which is critical in the context of aging and age-associated diseases. SIRT4 and SIRT5 regulate amino acid metabolism, nitrogen balance, and detoxification processes, further supporting metabolic efficiency and adaptation to nutrient availability [5, 6].

In the nucleus, SIRT6 and SIRT7 contribute to genome stability and ribosomal biogenesis. SIRT6 promotes DNA repair, telomere maintenance, and chromatin remodeling, all of which are essential for cellular longevity and protection against genomic instability. SIRT6 deficiency accelerates aging phenotypes, whereas its overexpression has been associated with lifespan extension in animal models. SIRT7 supports nucleolar function and has been implicated in maintaining cardiac and liver health [7].

The involvement of sirtuins in aging extends beyond their metabolic effects. They modulate key aging-related pathways, including inflammation, senescence, and proteostasis. Caloric restriction, a well-established intervention that delays aging and extends lifespan in various species, exerts many of its beneficial effects through sirtuin activation. This connection underscores the responsiveness of sirtuins to the cellular energy state and highlights their potential as therapeutic targets [8].

Pharmacological activation of sirtuins has garnered significant interest for promoting healthy aging and combating metabolic diseases. Compounds like resveratrol, a natural polyphenol, and synthetic SIRT1 activators have demonstrated beneficial effects in preclinical models, improving insulin sensitivity, mitochondrial function, and survival under metabolic stress. Although translating these findings into human therapies has proven challenging, ongoing research continues to explore sirtuin-targeted approaches for age-related conditions, including neurodegeneration, cardiovascular disease, and metabolic syndrome [9].

Despite their promise, the regulation of sirtuins is complex, influenced by NAD⁺ availability, post-translational modifications, and interactions with other metabolic regulators. NAD⁺ levels decline with age, which impairs sirtuin activity and contributes to metabolic dysfunction. Strategies aimed at boosting NAD⁺, such as supplementation with precursors like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), have shown potential in restoring sirtuin function and improving age-associated metabolic outcomes [10].

Conclusion

The exploration of cell structures provides profound insights into the functional complexity of life. Each organelle, membrane, and molecular framework contributes to a symphony of processes that sustain life. By delving deeper into these microscopic realms, scientists continue to unravel the mysteries of cellular function, paving the way for innovations in medicine, biotechnology, and beyond.

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