In line with a brand new research, a polyphenol-rich pure extract positively impacts lifespan, healthspan, and cellular senescence. These outcomes have been noticed in each cell tradition and a mouse mannequin [1].
From folks medication to fashionable science
Conventional and folks medicines supply many botanical extracts that may be examined by fashionable science for his or her medicinal properties and influences on growing old. One such plant is the Bolivian prawn sage (Salvia haenkei).
Salvia haenkei is a quick rising perennial plant with fragrant leaves and upright stems of pink, prawn-like flowers. It’s native to Bolivia and southern Peru and is discovered within the seasonally dry tropical setting of these nations.
This research’s authors had beforehand screened botanical extracts and found that an extract from Salvia haenkei delays cellular senescence in human cell cultures [2]. The extract is known as Haenkenium (HK).
Longer and more healthy lives
On this research, the authors administered HK to the ingesting water of 20-month-old mice till the ends of their lives. The mice that consumed HK lived longer than the management group: a median lifespan of 32.25 months in comparison with 28 months.
This lifespan impact was sex-independent, as each female and male mice handled with HK had longer lifespans. The researchers additionally reported no noticed indicators of toxicity.
Enhancements in lifespan have been accompanied by enhancements in healthspan, as HK-treated animals’ age-related phenotypes have been improved in comparison with the management group.
These phenotypes included irregular rounding of the higher again (kyphosis), tumor growth, fur high quality, bone construction, grip power, and kidney operate. In different phrases, not solely did the mice stay longer, they have been additionally more healthy.
Impacts on gene expression
The authors in contrast muscle-specific gene expression between younger and previous animals. In addition they analyzed the influence of HK remedy on age-related gene expression adjustments.
The evaluation recognized genes which might be upregulated and downregulated throughout growing old. In mice handled with HK, they noticed comparative downregulation of aging-upregulated genes and upregulation of aging-downregulated genes.
The researchers additionally famous the molecular pathways and processes of those age-related gene expression adjustments, which included irritation, immune activation, mobile senescence, and the senescence-associated secretory phenotype (SASP).
In mice handled with HK, these pathways have been comparatively suppressed. To make certain, the researchers used a number of strategies to verify these findings in several tissues.
Past growing old
Mobile senescence may end up from pure growing old or may be induced by stressors, reminiscent of chemotherapy [3]. Since HK was efficient in ameliorating the consequences of senescence brought on by growing old, the researchers hypothesized that it might be efficient in ameliorating the consequences of chemotherapy on senescence.
They handled the mice with doxorubicin, a potent chemotherapeutic agent that induces mobile senescence [4]. The mice handled with doxorubicin that additionally consumed water with HK had fewer amassed senescent cells and didn’t lose as a lot physique weight because the controls.
Doxorubicin can be recognized for inflicting cardiac dysfunction by inducing senescence in cardiac tissue [5]. On this research, the researchers induced senescence with doxorubicin in human-induced cardiomyocyte cells after which handled them with HK. HK remedy considerably decreased senescence in these cells. Nevertheless, as researchers warning, there may be nonetheless a necessity to check the influence of HK on persistent publicity to doxorubicin to higher replicate scientific settings.
Discovering the lively element
For the reason that HK extract has proven such promising outcomes, the researchers have been interested in which element of this botanical extract is chargeable for these results. They recognized a number of teams of molecules within the extract, together with phenols/lignans, flavonoids, and terpenes. Earlier analysis reported that flavonoids can modulate mobile senescence [6, 7]; the researchers determined to focus primarily on this group for additional exploration.
Testing a number of flavonoids current in HK revealed that three had an influence on senescence that have been just like general HK remedy. Amongst these three, luteolin and its derivatives account for 1.33% of the HK extract, making it essentially the most prevalent flavonoid.
Subsequent experiments, in cell tradition and mice, have proven that luteolin acted equally to HK in stopping the buildup of senescent cells after senescence induction by UV or doxorubicin, which means that luteolin is a key element of HK.
On the molecular degree, the researchers recognized that luteolin binds to the cell cycle regulator CDK6 and disrupts binding between the cell cycle inhibitor p16 and CDK6. The rise in p16 performs a component in growing senescence by blocking CDK6 exercise and inhibiting the cell cycle [8]. The researchers counsel that that is luteolin’s mechanism of motion in stopping or delaying the onset of senescence.
Strengths and weaknesses
Luteolin, recognized on this research as an lively compound with anti-senescence properties, isn’t solely present in HK however in lots of edible greens and herbs and has been described beforehand to have antioxidant, anti-inflammatory, and anticancer properties [9, 10], which makes it an attention-grabbing candidate for additional research and scientific trials.
The researchers level out that opposite to many research of various compounds, the dose they used is low, which makes it a promising candidate to be used as a complement or in prescription drugs. Moreover, these researchers have demonstrated that even remedy began comparatively later in life can nonetheless present many helpful results, which makes it promising for people. Nevertheless, the researchers targeted on a restricted variety of age-associated phenotypes, and additional analysis is required to evaluate if HK additionally impacts completely different points of growing old.
This paper targeted on luteolin and its anti-senescence properties, however different parts of HK can also considerably contribute to lifespan and healthspan extension, which requires additional investigation.
Lastly, the authors warning that their research concerned experiments carried out on inbred mice, and additional analysis ought to verify if these results are additionally noticed in a extra genetically heterogeneous inhabitants.
Literature
[1] Zumerle, S., Sarill, M., Saponaro, M., Colucci, M., Contu, L., Lazzarini, E., Sartori, R., Pezzini, C., Rinaldi, A., Scanu, A., Sgrignani, J., Locatelli, P., Sabbadin, M., Valdata, A., Brina, D., Giacomini, I., Rizzo, B., Pierantoni, A., Sharifi, S., . . . Alimonti, A. (2024). Concentrating on senescence induced by age or chemotherapy with a polyphenol-rich pure extract improves longevity and healthspan in mice. Nature Growing old.
[2] Matic, I., Revandkar, A., Chen, J., Bisio, A., Dall’Acqua, S., Cocetta, V., Brun, P., Mancino, G., Milanese, M., Mattei, M., Montopoli, M., & Alimonti, A. (2016). Identification of Salvia haenkei as gerosuppressant agent through the use of an built-in senescence-screening assay. Growing old, 8(12), 3223–3240.
[3] Demaria, M., O’Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, Ok., Le, C., Mitin, N., Deal, A. M., Alston, S., Academia, E. C., Kilmarx, S., Valdovinos, A., Wang, B., de Bruin, A., Kennedy, B. Ok., Melov, S., Zhou, D., Sharpless, N. E., … Campisi, J. (2017). Mobile Senescence Promotes Hostile Results of Chemotherapy and Most cancers Relapse. Most cancers discovery, 7(2), 165–176.
[4] Ludke, A., Akolkar, G., Ayyappan, P., Sharma, A. Ok., & Singal, P. Ok. (2017). Time course of adjustments in oxidative stress and stress-induced proteins in cardiomyocytes uncovered to doxorubicin and prevention by vitamin C. PloS one, 12(7), e0179452.
[5] Lazzarini, E., Lodrini, A. M., Arici, M., Bolis, S., Vagni, S., Panella, S., Rendon-Angel, A., Saibene, M., Metallo, A., Torre, T., Vassalli, G., Ameri, P., Altomare, C., Rocchetti, M., & Barile, L. (2022). Stress-induced untimely senescence is related to a chronic QT interval and recapitulates options of cardiac growing old. Theranostics, 12(11), 5237–5257.
[6] Fan, X., Fan, Z., Yang, Z., Huang, T., Tong, Y., Yang, D., Mao, X., & Yang, M. (2022). Flavonoids-Pure Presents to Promote Well being and Longevity. Worldwide journal of molecular sciences, 23(4), 2176.
[7] Lim, H., Park, H., & Kim, H. P. (2015). Results of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts. Biochemical pharmacology, 96(4), 337–348.
[8] Campisi, J., & d’Adda di Fagagna, F. (2007). Mobile senescence: when unhealthy issues occur to good cells. Nature opinions. Molecular cell biology, 8(9), 729–740.
[9] Gendrisch, F., Esser, P. R., Schempp, C. M., & Wölfle, U. (2021). Luteolin as a modulator of pores and skin growing old and irritation. BioFactors (Oxford, England), 47(2), 170–180.
[10] Seelinger, G., Merfort, I., Wölfle, U., & Schempp, C. M. (2008). Anti-carcinogenic results of the flavonoid luteolin. Molecules (Basel, Switzerland), 13(10), 2628–2651.
