Targeting senescent cells to extend lifespan

Although our understanding of the mechanisms underlying aging is limited, recent findings from animal studies indicate that targeting cellular senescence in vivo may prevent or alleviate age-related diseases.

Aging is a significant risk factor for numerous diseases, including cancer, metabolic disorders and neurodegeneration. Although the precise mechanisms underlying aging remain elusive, recent evidence from animal studies suggests that targeting cellular senescence may prevent or alleviate age-related pathologies.

Longevity.Technology: As we age, the ability of our bodies to regenerate and replace damaged cells gradually decreases, leading to the accumulation of senescent cells in organs and tissues. This means our ability to perform physiological functions also declines with aging, leading to an increased risk of disease development [1].

Cellular senescence is a physiological process involving the “aging” of our body’s cells, which can only proliferate for a limited number of times – also known as Hayflick limit. Although senescence acts as a brake, limiting the potential malignant transformation of damaged cells, cellular senescence has emerged as a hallmark of age-related pathologies. For instance, molecules secreted by senescent cells – collectively called senescence-associated secretory phenotype (SASP) – have been implicated in a wide range of disorders. Hence, targeting senescent cells using senolytics has gained increasing attention as a method to extend lifespan and healthspan [1, 2].

 


 

 

“…various stressors within mammalian tissues drive cellular senescence in vivo, contributing to the development of age-related diseases … various cell types may respond differently to these stressors, possibly forming the basis of tissue-specific pathologies associated with aging.”

 


 

 

Although our current knowledge about senescence is mostly derived from in vitro studies, scientists believe that the mechanisms involved in senescence differ considerably between cells growing in the laboratory and the cells in our tissues. These differences may significantly impact the outcomes of senolytics in clinical trials [1].

In a recent article published in the journal Mechanisms of Ageing and Development, Kumar et al. have indicated that various stressors within mammalian tissues drive cellular senescence in vivo, contributing to the development of age-related diseases. They also point out that various cell types may respond differently to these stressors, possibly forming the basis of tissue-specific pathologies associated with aging [1].

Therefore, a more in-depth understanding of the tissue- and cell type-specific changes associated with senescence in vivo is required before we are able to effectively target cellular senescence to treat age-related diseases and promote Longevity.

“If you add a senolytic that works perfectly to an old eye, and didn’t do anything else, I would bet you what you would end up with is blindness,” says Dr Richard Faragher, Professor of biological gerontology at the University of Brighton. “Because you would kill the senescent cells in the endothelial layer, and the only way you would be able to replace them is by the spreading of the survivors. So, I would argue, what we also need is the ability to take senescent cells and revert them to normal.”

Although the role of cellular senescence in aging and age-related diseases has become evident over the last years, the field is slowly moving due to the lack of reliable biomarkers to detect senescent cells in human tissues and organs. Only with the development of robust and accurate in vivo biomarkers of senescence will we be able to develop potent senolytics and accurately assess their efficacy in a clinical setting.

[1] https://www.sciencedirect.com/science/article/abs/pii/S0047637420301044
[2] https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(20)30085-2

Image credit: 3D Animation Production CompanyPixabay
Carla Heyworth
Carla is sub editor at Longevity.Technology and she's the glue that keeps the team on track and the articles rolling-out. She has an extensive background in B2B communications, events and marketing. Carla's a visual person and can often be found behind a camera or editing photos

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