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抗衰老是怎么回事?如何抗衰老

衰老是一個(gè)多種因素相互作用的過程,而且任何干預(yù)措施都無法阻止其進(jìn)程。

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衰老和抗衰老真正的工作原理是什么?圖片來源:GETTY IMAGES

在你認(rèn)識(shí)的人當(dāng)中,可能有人不怎么顯老,而且看起來比其實(shí)際年齡年輕很多歲。不過可能也有人異常顯老,其身體和思想似乎飽受歲月的摧殘。為什么一些人在退休后過的順風(fēng)順?biāo)?,但有的人卻備受病痛折磨。

在我整個(gè)科學(xué)工作生涯中,我一直從事衰老方面的研究,而且我在密歇根大學(xué)(University of Michigan)教授衰老方面的細(xì)胞和分子生物學(xué)。衰老研究的出發(fā)點(diǎn)并非是尋找一款萬能藥,來治療那些可能困擾老年人的疾病。過去一二十年的研究顯示,衰老是一個(gè)多種因素相互作用的過程,而且任何干預(yù)措施都無法阻止其進(jìn)程。

什么是衰老?

衰老的定義有很多,但科學(xué)家普遍認(rèn)為其具有以下共同特征:衰老是一個(gè)需要時(shí)間的過程,會(huì)讓身體變得更容易生病、受傷和死亡。這個(gè)過程受到內(nèi)部因素和外部因素的影響,內(nèi)部因素是你自己身體出現(xiàn)的新問題,而外部因素則是環(huán)境給人體器官帶來的傷害。

你的身體由數(shù)萬億個(gè)細(xì)胞構(gòu)成,而且每一個(gè)細(xì)胞不僅要負(fù)責(zé)其所在組織的一項(xiàng)或多項(xiàng)專屬功能,同時(shí)還得盡可能地讓自身存活。這其中包括代謝營(yíng)養(yǎng)物質(zhì),排出廢棄物,與其他細(xì)胞交換信號(hào),以及適應(yīng)壓力。

問題在于,細(xì)胞里的每一個(gè)單一流程和組件都可能會(huì)受到影響或破壞。因此,你的細(xì)胞每天都會(huì)消耗大量的能量,來預(yù)防、發(fā)現(xiàn)和修復(fù)這些問題。

衰老可以被認(rèn)為是內(nèi)穩(wěn)態(tài)(身體系統(tǒng)的一種平衡狀態(tài))維持能力的逐漸消失,它會(huì)導(dǎo)致身體無法預(yù)防或識(shí)別損傷和功能故障,或無法完全或迅速修復(fù)出現(xiàn)的問題。衰老則是上述問題共同作用的結(jié)果。數(shù)十年的研究顯示,幾乎所有的細(xì)胞流程都會(huì)隨著年齡的增長(zhǎng)而出現(xiàn)更多的損傷。

DNA修復(fù)與蛋白回收

細(xì)胞衰老領(lǐng)域的大多數(shù)研究都專注于研究DNA和蛋白質(zhì)如何隨著年紀(jì)的增長(zhǎng)而變化??茖W(xué)家還開始研究細(xì)胞中其他很多重要的生物分子在衰老方面所扮演的潛在角色。

細(xì)胞的一項(xiàng)重要工作就是維持其DNA,后者是細(xì)胞在生產(chǎn)特定蛋白質(zhì)時(shí)所必須遵從的說明書。DNA維護(hù)涉及保護(hù)和精準(zhǔn)修復(fù)遺傳物質(zhì)和相關(guān)分子出現(xiàn)的損傷。

蛋白質(zhì)是細(xì)胞內(nèi)部的工人。它們會(huì)執(zhí)行化學(xué)反應(yīng),提供結(jié)構(gòu)支持,發(fā)送和接受信息,保留和釋放能量等等。如果蛋白質(zhì)受損,細(xì)胞就會(huì)使用涉及特定蛋白質(zhì)的機(jī)制,這種機(jī)制要么會(huì)嘗試修復(fù)破損蛋白,要么會(huì)對(duì)蛋白進(jìn)行回收操作。類似的機(jī)制還會(huì)把不相關(guān)的蛋白藏起來,或在不需要時(shí)將其銷毀。這樣,細(xì)胞的組件隨后便能夠被用于制造新的蛋白質(zhì)。

衰老會(huì)干擾復(fù)雜的生物網(wǎng)絡(luò)

細(xì)胞內(nèi)部組件之間、單個(gè)細(xì)胞之間、器官與環(huán)境之間的串?dāng)_構(gòu)成了一個(gè)復(fù)雜、不斷變化的信息網(wǎng)絡(luò)。

當(dāng)負(fù)責(zé)制作和維護(hù)DNA的所有流程和蛋白質(zhì)功能都可以正常運(yùn)轉(zhuǎn)時(shí),細(xì)胞內(nèi)部肩負(fù)特定任務(wù)的不同部門(稱為胞器)能夠維護(hù)細(xì)胞的健康和功能。要想器官正常工作,那么構(gòu)成該器官的大部分細(xì)胞就都得正常工作。如果整個(gè)生命體要想存活和不斷生長(zhǎng),那么其機(jī)體的所有器官就都得正常工作。

衰老可能會(huì)導(dǎo)致上述任意一個(gè)層面出現(xiàn)功能紊亂,從亞細(xì)胞一直到整個(gè)生命體。有時(shí)候,一個(gè)負(fù)責(zé)對(duì)重要DNA修復(fù)蛋白進(jìn)行編碼的基因受到損害,那么細(xì)胞內(nèi)其他所有基因在修復(fù)時(shí)出錯(cuò)的概率就會(huì)更高。還有的時(shí)候,細(xì)胞的回收系統(tǒng)無法再降解功能紊亂的組件。更有甚者,細(xì)胞、組織和器官之間的溝通系統(tǒng)會(huì)遭到破壞,繼而削弱生命體應(yīng)對(duì)機(jī)體內(nèi)變化的能力。

隨機(jī)出現(xiàn)的因素可能會(huì)不斷增加分子的負(fù)擔(dān),而且隨著時(shí)間的推移會(huì)導(dǎo)致未能完全修復(fù)的細(xì)胞損傷越來越多。隨著這種損傷的積累,本應(yīng)用于修復(fù)這個(gè)問題的各個(gè)系統(tǒng)也會(huì)積累傷病。隨著細(xì)胞的老化,這一現(xiàn)象會(huì)導(dǎo)致身體出現(xiàn)越來越多的損耗,而且周而復(fù)始。

抗衰老干預(yù)舉措

生命體細(xì)胞流程的獨(dú)立性是一把雙刃劍:只要一個(gè)流程遭到徹底破壞,那么所有與其互動(dòng)或存在依賴關(guān)系的其他流程也會(huì)受損。然而,這種內(nèi)部的互連還意味著提振其中一個(gè)高度互連的流程亦可以改善相關(guān)功能。事實(shí)上,這也正是最有效抗衰老干預(yù)舉措的工作原理。

盡管在阻止衰老方面沒有什么靈丹妙藥,但某些干預(yù)在實(shí)驗(yàn)室中似乎能夠延緩衰老。盡管目前已經(jīng)有臨床試驗(yàn)在人體上嘗試不同的抗衰老方式,但大多數(shù)現(xiàn)有數(shù)據(jù)都來自于動(dòng)物,例如線蟲、蒼蠅、老鼠和非人靈長(zhǎng)類動(dòng)物。

研究的最多的一種干預(yù)是熱量限制,它涉及減少動(dòng)物正常飲食的熱量,但不會(huì)剝奪必須營(yíng)養(yǎng)物。有一款藥物名為雷帕霉素,已經(jīng)獲得美國(guó)食品與藥品管理局(FDA)的批準(zhǔn),用于器官移植和治療某些癌癥。這款藥物發(fā)揮作用的方式至少與熱量限制激活細(xì)胞的路徑十分接近。這兩種方式都會(huì)影響其信號(hào)中心,繼而引導(dǎo)細(xì)胞保存其現(xiàn)有的生物分子而不是壯大和制造新的生物分子。隨著時(shí)間的推移,這個(gè)細(xì)胞層面的“減少、重新利用、循環(huán)”會(huì)消除受損組件,并留下更高比例的正常功能組件。

其他干預(yù)措施包括改變某些代謝物的水平,有選擇地破壞停止分裂的老化細(xì)胞,改變腸道微生物群和行為矯正。

這些干預(yù)的共同之處在于,它們會(huì)影響對(duì)于細(xì)胞內(nèi)穩(wěn)態(tài)維持至關(guān)重要的核心流程。這些流程往往會(huì)隨著年齡的增長(zhǎng)而變得失調(diào)或出現(xiàn)障礙,而且與其他細(xì)胞維護(hù)系統(tǒng)息息相關(guān)。通常,這些流程是機(jī)體內(nèi)DNA和蛋白質(zhì)保護(hù)機(jī)制的核心引擎。

衰老并非由單一因素導(dǎo)致。每個(gè)人的衰老進(jìn)程都是獨(dú)一無二的,的確,每個(gè)細(xì)胞亦是如此。隨著時(shí)間的推移,有無數(shù)個(gè)因素會(huì)導(dǎo)致你的基本生物機(jī)制出現(xiàn)錯(cuò)誤,而這些因素的疊加將造就一張個(gè)人獨(dú)有的衰老因素關(guān)系網(wǎng),這也是為什么打造萬能型抗衰老方案具有莫大挑戰(zhàn)性。

盡管如此,研究同時(shí)針對(duì)多個(gè)重要細(xì)胞流程的干預(yù)舉措可以幫助人們?cè)谝簧懈L(zhǎng)的時(shí)間內(nèi)改善和維持健康。在這一過程中,這些進(jìn)步可能會(huì)幫助延長(zhǎng)人們的壽命。(財(cái)富中文網(wǎng))

本文作者艾倫·夸爾斯(Ellen Quarles)是密歇根大學(xué)(University of Michigan)分子、細(xì)胞和發(fā)育生物學(xué)副教授。

本文已獲知識(shí)共享(Creative Commons)組織的許可,轉(zhuǎn)載自The Conversation網(wǎng)站。

譯者:馮豐

審校:夏林

在你認(rèn)識(shí)的人當(dāng)中,可能有人不怎么顯老,而且看起來比其實(shí)際年齡年輕很多歲。不過可能也有人異常顯老,其身體和思想似乎飽受歲月的摧殘。為什么一些人在退休后過的順風(fēng)順?biāo)?,但有的人卻備受病痛折磨。

在我整個(gè)科學(xué)工作生涯中,我一直從事衰老方面的研究,而且我在密歇根大學(xué)(University of Michigan)教授衰老方面的細(xì)胞和分子生物學(xué)。衰老研究的出發(fā)點(diǎn)并非是尋找一款萬能藥,來治療那些可能困擾老年人的疾病。過去一二十年的研究顯示,衰老是一個(gè)多種因素相互作用的過程,而且任何干預(yù)措施都無法阻止其進(jìn)程。

什么是衰老?

衰老的定義有很多,但科學(xué)家普遍認(rèn)為其具有以下共同特征:衰老是一個(gè)需要時(shí)間的過程,會(huì)讓身體變得更容易生病、受傷和死亡。這個(gè)過程受到內(nèi)部因素和外部因素的影響,內(nèi)部因素是你自己身體出現(xiàn)的新問題,而外部因素則是環(huán)境給人體器官帶來的傷害。

你的身體由數(shù)萬億個(gè)細(xì)胞構(gòu)成,而且每一個(gè)細(xì)胞不僅要負(fù)責(zé)其所在組織的一項(xiàng)或多項(xiàng)專屬功能,同時(shí)還得盡可能地讓自身存活。這其中包括代謝營(yíng)養(yǎng)物質(zhì),排出廢棄物,與其他細(xì)胞交換信號(hào),以及適應(yīng)壓力。

問題在于,細(xì)胞里的每一個(gè)單一流程和組件都可能會(huì)受到影響或破壞。因此,你的細(xì)胞每天都會(huì)消耗大量的能量,來預(yù)防、發(fā)現(xiàn)和修復(fù)這些問題。

衰老可以被認(rèn)為是內(nèi)穩(wěn)態(tài)(身體系統(tǒng)的一種平衡狀態(tài))維持能力的逐漸消失,它會(huì)導(dǎo)致身體無法預(yù)防或識(shí)別損傷和功能故障,或無法完全或迅速修復(fù)出現(xiàn)的問題。衰老則是上述問題共同作用的結(jié)果。數(shù)十年的研究顯示,幾乎所有的細(xì)胞流程都會(huì)隨著年齡的增長(zhǎng)而出現(xiàn)更多的損傷。

DNA修復(fù)與蛋白回收

細(xì)胞衰老領(lǐng)域的大多數(shù)研究都專注于研究DNA和蛋白質(zhì)如何隨著年紀(jì)的增長(zhǎng)而變化??茖W(xué)家還開始研究細(xì)胞中其他很多重要的生物分子在衰老方面所扮演的潛在角色。

細(xì)胞的一項(xiàng)重要工作就是維持其DNA,后者是細(xì)胞在生產(chǎn)特定蛋白質(zhì)時(shí)所必須遵從的說明書。DNA維護(hù)涉及保護(hù)和精準(zhǔn)修復(fù)遺傳物質(zhì)和相關(guān)分子出現(xiàn)的損傷。

蛋白質(zhì)是細(xì)胞內(nèi)部的工人。它們會(huì)執(zhí)行化學(xué)反應(yīng),提供結(jié)構(gòu)支持,發(fā)送和接受信息,保留和釋放能量等等。如果蛋白質(zhì)受損,細(xì)胞就會(huì)使用涉及特定蛋白質(zhì)的機(jī)制,這種機(jī)制要么會(huì)嘗試修復(fù)破損蛋白,要么會(huì)對(duì)蛋白進(jìn)行回收操作。類似的機(jī)制還會(huì)把不相關(guān)的蛋白藏起來,或在不需要時(shí)將其銷毀。這樣,細(xì)胞的組件隨后便能夠被用于制造新的蛋白質(zhì)。

衰老會(huì)干擾復(fù)雜的生物網(wǎng)絡(luò)

細(xì)胞內(nèi)部組件之間、單個(gè)細(xì)胞之間、器官與環(huán)境之間的串?dāng)_構(gòu)成了一個(gè)復(fù)雜、不斷變化的信息網(wǎng)絡(luò)。

當(dāng)負(fù)責(zé)制作和維護(hù)DNA的所有流程和蛋白質(zhì)功能都可以正常運(yùn)轉(zhuǎn)時(shí),細(xì)胞內(nèi)部肩負(fù)特定任務(wù)的不同部門(稱為胞器)能夠維護(hù)細(xì)胞的健康和功能。要想器官正常工作,那么構(gòu)成該器官的大部分細(xì)胞就都得正常工作。如果整個(gè)生命體要想存活和不斷生長(zhǎng),那么其機(jī)體的所有器官就都得正常工作。

衰老可能會(huì)導(dǎo)致上述任意一個(gè)層面出現(xiàn)功能紊亂,從亞細(xì)胞一直到整個(gè)生命體。有時(shí)候,一個(gè)負(fù)責(zé)對(duì)重要DNA修復(fù)蛋白進(jìn)行編碼的基因受到損害,那么細(xì)胞內(nèi)其他所有基因在修復(fù)時(shí)出錯(cuò)的概率就會(huì)更高。還有的時(shí)候,細(xì)胞的回收系統(tǒng)無法再降解功能紊亂的組件。更有甚者,細(xì)胞、組織和器官之間的溝通系統(tǒng)會(huì)遭到破壞,繼而削弱生命體應(yīng)對(duì)機(jī)體內(nèi)變化的能力。

隨機(jī)出現(xiàn)的因素可能會(huì)不斷增加分子的負(fù)擔(dān),而且隨著時(shí)間的推移會(huì)導(dǎo)致未能完全修復(fù)的細(xì)胞損傷越來越多。隨著這種損傷的積累,本應(yīng)用于修復(fù)這個(gè)問題的各個(gè)系統(tǒng)也會(huì)積累傷病。隨著細(xì)胞的老化,這一現(xiàn)象會(huì)導(dǎo)致身體出現(xiàn)越來越多的損耗,而且周而復(fù)始。

抗衰老干預(yù)舉措

生命體細(xì)胞流程的獨(dú)立性是一把雙刃劍:只要一個(gè)流程遭到徹底破壞,那么所有與其互動(dòng)或存在依賴關(guān)系的其他流程也會(huì)受損。然而,這種內(nèi)部的互連還意味著提振其中一個(gè)高度互連的流程亦可以改善相關(guān)功能。事實(shí)上,這也正是最有效抗衰老干預(yù)舉措的工作原理。

盡管在阻止衰老方面沒有什么靈丹妙藥,但某些干預(yù)在實(shí)驗(yàn)室中似乎能夠延緩衰老。盡管目前已經(jīng)有臨床試驗(yàn)在人體上嘗試不同的抗衰老方式,但大多數(shù)現(xiàn)有數(shù)據(jù)都來自于動(dòng)物,例如線蟲、蒼蠅、老鼠和非人靈長(zhǎng)類動(dòng)物。

研究的最多的一種干預(yù)是熱量限制,它涉及減少動(dòng)物正常飲食的熱量,但不會(huì)剝奪必須營(yíng)養(yǎng)物。有一款藥物名為雷帕霉素,已經(jīng)獲得美國(guó)食品與藥品管理局(FDA)的批準(zhǔn),用于器官移植和治療某些癌癥。這款藥物發(fā)揮作用的方式至少與熱量限制激活細(xì)胞的路徑十分接近。這兩種方式都會(huì)影響其信號(hào)中心,繼而引導(dǎo)細(xì)胞保存其現(xiàn)有的生物分子而不是壯大和制造新的生物分子。隨著時(shí)間的推移,這個(gè)細(xì)胞層面的“減少、重新利用、循環(huán)”會(huì)消除受損組件,并留下更高比例的正常功能組件。

其他干預(yù)措施包括改變某些代謝物的水平,有選擇地破壞停止分裂的老化細(xì)胞,改變腸道微生物群和行為矯正。

這些干預(yù)的共同之處在于,它們會(huì)影響對(duì)于細(xì)胞內(nèi)穩(wěn)態(tài)維持至關(guān)重要的核心流程。這些流程往往會(huì)隨著年齡的增長(zhǎng)而變得失調(diào)或出現(xiàn)障礙,而且與其他細(xì)胞維護(hù)系統(tǒng)息息相關(guān)。通常,這些流程是機(jī)體內(nèi)DNA和蛋白質(zhì)保護(hù)機(jī)制的核心引擎。

衰老并非由單一因素導(dǎo)致。每個(gè)人的衰老進(jìn)程都是獨(dú)一無二的,的確,每個(gè)細(xì)胞亦是如此。隨著時(shí)間的推移,有無數(shù)個(gè)因素會(huì)導(dǎo)致你的基本生物機(jī)制出現(xiàn)錯(cuò)誤,而這些因素的疊加將造就一張個(gè)人獨(dú)有的衰老因素關(guān)系網(wǎng),這也是為什么打造萬能型抗衰老方案具有莫大挑戰(zhàn)性。

盡管如此,研究同時(shí)針對(duì)多個(gè)重要細(xì)胞流程的干預(yù)舉措可以幫助人們?cè)谝簧懈L(zhǎng)的時(shí)間內(nèi)改善和維持健康。在這一過程中,這些進(jìn)步可能會(huì)幫助延長(zhǎng)人們的壽命。(財(cái)富中文網(wǎng))

本文作者艾倫·夸爾斯(Ellen Quarles)是密歇根大學(xué)(University of Michigan)分子、細(xì)胞和發(fā)育生物學(xué)副教授。

本文已獲知識(shí)共享(Creative Commons)組織的許可,轉(zhuǎn)載自The Conversation網(wǎng)站。

譯者:馮豐

審校:夏林

You likely know someone who seems to age slowly, appearing years younger than their birth date suggests. And you likely have seen the opposite – someone whose body and mind seem much more ravaged by time than others. Why do some people seem to glide though their golden years and others physiologically struggle in midlife?

I have worked in the field of aging for all of my scientific career, and I teach the cellular and molecular biology of aging at the University of Michigan. Aging research doesn’t tend to be about finding the one cure that fixes all that may ail you in old age. Instead, the last decade or two of work points to aging as a multi-factoral process – and no single intervention can stop it all.

What is aging?

There are many different definitions of aging, but scientists generally agree upon some common features: Aging is a time-dependent process that results in increased vulnerability to disease, injury and death. This process is both intrinsic, when your own body causes new problems, and extrinsic, when environmental insults damage your tissues.

Your body is comprised of trillions of cells, and each one is not only responsible for one or more functions specific to the tissue it resides in, but must also do all the work of keeping itself alive. This includes metabolizing nutrients, getting rid of waste, exchanging signals with other cells and adapting to stress.

The trouble is that every single process and component in each of your cells can be interrupted or damaged. So your cells spend a lot of energy each day preventing, recognizing and fixing those problems.

Aging can be thought of as a gradual loss of the ability to maintain homeostasis – a state of balance among body systems – either by not being able to prevent or recognize damage and poor function, or by not adequately or rapidly fixing problems as they occur. Aging results from a combination of these issues. Decades of research has shown that nearly every cellular process becomes more impaired with age.

Repairing DNA and recycling proteins

Most research on cellular aging focuses on studying how DNA and proteins change with age. Scientists are also beginning to address the potential roles many other important biomolecules in the cell play in aging as well.

One of the cell’s chief jobs is to maintain its DNA – the instruction manual a cell’s machinery reads to produce specific proteins. DNA maintenance involves protecting against, and accurately repairing, damage to genetic material and the molecules binding to it.

Proteins are the workers of the cell. They perform chemical reactions, provide structural support, send and receive messages, hold and release energy, and much more. If the protein is damaged, the cell uses mechanisms involving special proteins that either attempt to fix the broken protein or send it off for recycling. Similar mechanisms tuck proteins out of the way or destroy them when they are no longer needed. That way, its components can be used later to build a new protein.

Aging disrupts a delicate biological network

The cross-talk between the components inside cells, cells as a whole, organs and the environment is a complex and ever-changing network of information.

When all processes involved in creating and maintaining DNA and protein function are working normally, the different compartments within a cell serving specialized roles – called organelles – can maintain the cell’s health and function. For an organ to work well, the majority of the cells that make it up need to function well. And for a whole organism to survive and thrive, all of the organs in its body need to work well.

Aging can lead to dysfunction at any of these levels, from the sub-cellular to the organismal. Maybe a gene encoding an important protein for DNA repair has become damaged, and now all of the other genes in the cell are more likely to be repaired incorrectly. Or perhaps the cell’s recycling systems are unable to degrade dysfunctional components anymore. Even the communication systems between cells, tissues and organs can become compromised, leaving the organism less able to respond to changes within the body.

Random chance can lead to a growing burden of molecular and cellular damage that is progressively less well-repaired over time. As this damage accumulates, the systems that are meant to fix it are accruing damage as well. This leads to a cycle of increasing wear and tear as cells age.

Anti-aging interventions

The interdependence of life’s cellular processes is a double-edged sword: Sufficiently damage one process, and all the other processes that interact with or depend on it become impaired. However, this interconnection also means that bolstering one highly interconnected process could improve related functions as well. In fact, this is how the most successful anti-aging interventions work.

There is no silver bullet to stop aging, but certain interventions do seem to slow aging in the laboratory. While there are ongoing clinical trials investigating different approaches in people, most existing data comes from animals like nematodes, flies, mice and nonhuman primates.

One of the best studied interventions is caloric restriction, which involves reducing the amount of calories an animal would normally eat without depriving them of necessary nutrients. An FDA-approved drug used in organ transplantation and some cancer treatments called rapamycin seems to work by using at least a subset of the same pathways that calorie restriction activates in the cell. Both affect signaling hubs that direct the cell to preserve the biomolecules it has rather than growing and building new biomolecules. Over time, this cellular version of “reduce, reuse, recycle” removes damaged components and leaves behind a higher proportion of functional components.

Other interventions include changing the levels of certain metabolites, selectively destroying senescent cells that have stopped dividing, changing the gut microbiome and behavioral modifications.

What all of these interventions have in common is that they affect core processes that are critical for cellular homeostasis, often become dysregulated or dysfunctional with age and are connected to other cellular maintenance systems. Often, these processes are the central drivers for mechanisms that protect DNA and proteins in the body.

There is no single cause of aging. No two people age the same way, and indeed, neither do any two cells. There are countless ways for your basic biology to go wrong over time, and these add up to create a unique network of aging-related factors for each person that make finding a one-size-fits-all anti-aging treatment extremely challenging.

However, researching interventions that target multiple important cellular processes simultaneously could help improve and maintain health for a greater portion of life. These advances could help people live longer lives in the process.

Ellen Quarles is Assistant Professor in Molecular, Cellular, and Developmental Biology, University of Michigan.

This article is republished from The Conversation under a Creative Commons license.

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