CRISPR Identifies KAT7 as a Secret Weapon to Reverse Aging.

In their search for the elusive fountain of youth, scientists have made significant progress in comprehending the complex processes involved in aging. A novel study that made use of CRISPR-Cas9 technology has revealed that the histone acetyltransferase gene KAT7 is a powerful inducer of cellular senescence. This finding not only clarifies the intricate process of aging but also provides access to possible interventions that might undo the effects of aging. Let’s examine this remarkable discovery in more detail.

Unraveling the Mysteries of Cellular Senescence

While the link between cellular senescence and aging has been established, the underlying mechanisms have remained largely enigmatic. To unravel these mysteries, researchers conducted a genome-wide CRISPR-Cas9–based screen using human mesenchymal precursor cells (hMPCs) with mutations associated with premature aging diseases such as Werner syndrome and Hutchinson-Gilford progeria syndrome.

KAT7 Emerges as a Senescence Driver

Among the myriad of genes investigated, KAT7 emerged as a key player in driving cellular senescence. KAT7, a histone acetyltransferase, plays a crucial role in modifying histones, the proteins that package DNA. Inactivation of KAT7 in mice, both aging normally and those with accelerated aging conditions, resulted in a remarkable extension of their lifespan.

The Ripple Effect: Impact on Histone Acetylation and Senescence

Further exploration revealed that inactivation of KAT7 led to a decrease in histone H3 lysine 14 acetylation, a modification associated with gene regulation. Importantly, this modification repressed the transcription of p15INK4b, a protein linked to cellular senescence. This cascade of events ultimately alleviated senescence in hMPCs.

Extending the Lifespan: CRISPR-Cas9 Intervention

Taking the findings a step further, researchers employed CRISPR-Cas9 technology to target KAT7 in vivo. Lentiviral vectors carrying Cas9/sg-Kat7 were administered intravenously, effectively alleviating hepatocyte senescence and liver aging in mice. This intervention not only showcased the potential of CRISPR-based genetic screening but also demonstrated its efficacy in extending the lifespan of both physiologically aged mice and progeroid mice exhibiting premature aging.

Implications for Aging Interventions

The study underscores the importance of understanding the genetic and epigenetic foundations of cellular senescence. By pinpointing KAT7 as a critical driver of aging, this research opens avenues for developing targeted interventions to slow down the aging process. The success of CRISPR-Cas9–based screens in identifying senescence-related genes highlights the potential for therapeutic breakthroughs in the field of aging research.

The discovery that KAT7 is a major contributor to cellular senescence represents a major advancement in the never-ending quest to combat aging. This innovative study provides hope for future interventions while also expanding our knowledge of the aging process. The possibility of stopping the aging process materializes as we decipher the genetic code, putting us one step closer to the fountain of youth.

References:

J. M. van Deursen, The role of senescent cells in ageing. Nature 509, 439–446 (2014).