The study found anti-aging compounds

individual aging is accompanied by a gradual decline in the body's various biological functions, one of the important features of which is the accumulation of senescies in the body. Aging cells themselves have dysfunction and secrete a variety of inflammatory and cytokines that cause tissue disorders and accelerate the aging process.
, selective removal of senescies in the body has become an important direction of anti-aging research. Reported compounds that remove senescies mainly induce the death of senescing cells by inhibiting the anti-apoptosis path path.
, however, there are obvious limitations to these compounds. First, the broad spectrum is not strong, different types of aging cells activate different anti-apoptosis path, so targeting specific anti-apoptosis path path, small molecules, can not effectively remove many types of aging cells in the body;
, how to specificly remove the accumulation of senescing cells from multiple tissue organs in the body is a key challenge.
April 27th, Deng Hongkui of Peking University's School of Life Sciences, in collaboration with Luo Weiping of the School of Chemistry and Molecular Engineering, published online advances in the journal Cell Research on the progress of aging cells. Aiming at the important characteristics of senescing cells, the research team cleverly designed and synthesized a new compound, which proved that the compound can effectively remove the accumulated senescing cells of multiple tissue organs in aging individuals, significantly improve the physiological state of elderly mice, and restore the body function of elderly mice.In older mice, SSK1 can be selectively activated by β-gal cutting of senescing cells, specifically removing senescing cells from the body, reducing aging-related characteristics, alleviating chronic inflammation, and restoring physiological function in older mice. Photo The team developed a new strategy
remove senescing cells in this work at Peking University's School of Life Sciences. Using the activity of the enhanced lysosome β-semi-lactosease (β-gal), the strategy designs and synthesizes a new anti-aging compound, SSK1, that can be specifically activated by the metabolism of the senescing cell β-semi-lactose glycosidease (SA-β-gal). SSK1 itself does not have a lethal effect, when it enters senescing cells, SSK1's β-semi-lactose glycoside bonds will be quickly cut by SA-β-gal, releasing deadly toxic molecules that induce the death of senescing cells β, and when SSK1 enters non-aging cells, SSK1 will not be metabolized due to its low activity and will not produce lethal effects.
team first demonstrated SSK1's ability to efficiently remove multiple types of senescing cells without affecting normal cell survival through in vitro cell experiments, demonstrating the broad-spectrum and specificity of the new small molecular compounds to remove senescing cells.
further tested the effects of the new small molecule compound in the body to remove senescies and anti-aging effects.
, SSK1 can significantly reduce the number of aging cells in multiple tissue organs in aging mice and reverse the gene expression spectrum associated with aging.
, SSK1 significantly reduces a variety of inflammatory factors and cytokines (SASPs) secreted by senescing cells in tissues and blood systems, and relieves chronic inflammation associated with aging.
Further systematic functional testing found that in older mice treated with SSK1, a variety of aging-related functional degradation (decreased motor endurance, reduced muscle strength, poor balance and reduced spontaneous exploration) was significantly improved, significantly better than reported compounds to remove senescies. The team also systematically tested the safety of SSK1 and found that even high doses of SSK1 did not have significant toxic side effects.
This study is the first to demonstrate the specificity and broadspectrality of SSK1, a new generation of small molecule compound designed for senesic cells β-semi-lactose glycosidease, which can effectively reduce aging symptoms in older mice, significantly improve physiological function in older mice, and provide a new way for anti-aging drug research and development.
the work was supported by the National Natural Science Foundation of China, the National Key Research and Development Program, and the Peking University-Tsinghua Joint Center for Life Sciences. (Source: Zhang Qingdan, China Science Daily)
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