SIRT7

SIRT7 is one of the seven mammalian sirtuins, proteins inspired by the yeast Sir2 gene known for their roles in longevity, metabolism, and stress resistance. As a member of this family, SIRT7 is a NAD+-dependent deacetylase, primarily localized in the nucleolus, and is implicated in various cellular processes including stress responses, DNA repair, apoptosis, and aging.

Genetic Expression and Regulation

SIRT7 gene expression is regulated by multiple factors including nutritional status and stress signals. It is typically upregulated in response to caloric restriction, a condition known to extend lifespan in various organisms. Its activity is also modulated by NAD+ levels, reflecting the metabolic state of the cell and linking SIRT7's function to the organism's overall metabolic and energy status.

Role in Longevity and Aging

SIRT7 influences longevity through several mechanisms. It has been shown to enhance stress resistance and genome stability, two factors important in aging and age-related diseases. SIRT7 deficiency in mice leads to shortened lifespan and an increased incidence of age-related pathologies, indicating its protective role against aging.

Chromatin Remodeling and Transcription Regulation

SIRT7 deacetylates histones and other nuclear proteins, affecting chromatin structure and thereby regulating gene expression. This includes genes involved in aging, stress response, and metabolic processes. By maintaining proper gene expression and genome integrity, SIRT7 contributes to cellular homeostasis and longevity.

Interactions with Other Sirtuins

SIRT7 interacts with other sirtuins, particularly SIRT1 and SIRT6, in various cellular processes. These interactions often have synergistic effects on longevity, stress resistance, and metabolism. Understanding these interactions is crucial for a holistic view of the sirtuin family's role in aging and longevity.

Involvement in Diseases

SIRT7's involvement in longevity and stress resistance also implicates it in various diseases, particularly those related to aging and metabolic dysregulation.

Cancer

SIRT7 has both tumor-promoting and tumor-suppressing activities, depending on the context and cancer type. It is involved in DNA repair and the stress response, processes that, when dysregulated, can lead to cancer development. Its exact role in cancer is complex and remains a topic of significant research.

Cardiovascular Diseases

SIRT7's role in lipid and cholesterol metabolism suggests its involvement in cardiovascular diseases. By regulating genes involved in lipid homeostasis and inflammation, SIRT7 may influence the development and progression of atherosclerosis and other cardiovascular conditions.

Metabolic Disorders

Through its impact on metabolism and energy homeostasis, SIRT7 is implicated in metabolic disorders such as obesity and diabetes. Its activity affects insulin secretion, fat storage, and overall metabolic rate, making it a potential target for therapeutic interventions in metabolic diseases.

Research and Therapeutic Potential

Ongoing research is unraveling the complex roles of SIRT7 in longevity, metabolism, and disease. As a central player in aging-related processes, SIRT7 is a potential target for therapies aimed at age-related diseases and lifespan extension.

Drug Discovery and SIRT7 Modulators

Identifying molecules that can modulate SIRT7 activity is a key area of research. These modulators have the potential to treat or prevent diseases associated with aging and metabolism by restoring or enhancing SIRT7 function.

Challenges and Future Directions

The multifaceted role of SIRT7 presents both opportunities and challenges for therapeutic development. Future research will need to address the complex interplay between SIRT7, other sirtuins, and various cellular pathways to harness its therapeutic potential fully.

Todo

2024, SIRT7: the seventh key to unlocking the mystery of aging ^[1]

References

↑ Raza U et al.: SIRT7: the seventh key to unlocking the mystery of aging. Physiol Rev 2024. (PMID 37676263) [PubMed] [DOI] Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.

[pmid37676263-1] Raza U et al.: SIRT7: the seventh key to unlocking the mystery of aging. Physiol Rev 2024. (PMID 37676263) [PubMed] [DOI] Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.

[1]