GLP-1 may slow biological aging
本文为原文前 6,000 字符的节选翻译，完整内容请查看原文。
Beyond the widespread attention GLP-1 drugs are receiving for treating obesity, lowering blood sugar and decreasing the risk of cardiovascular disease, emerging research is investigating their other potential impacts — including their effects on aging.
除了 GLP-1 药物在治疗肥胖、降低血糖和降低心血管疾病风险方面受到广泛关注外，新兴研究正在调查其其他潜在影响，包括对衰老的影响。
Now, a new study provides the first randomized, placebo-controlled clinical evidence that semaglutide, a widely used GLP-1 drug, slows down the accumulation of biological aging markers in the DNA of adults with HIV. The study is published in Nature Communications.
目前，一项新的研究提供了首个随机、安慰剂对照的临床证据，表明广泛使用的 GLP-1 药物司美格鲁肽（semaglutide）可以减缓艾滋病毒（HIV）感染者 DNA 中生物衰老标志物的积累。该研究发表在《自然-通讯》（Nature Communications）杂志上。
Researchers at the University of California, San Diego and several partner institutions analyzed data from a previously published clinical trial of 108 adults with HIV‑associated lipohypertrophy, a condition in which excess fat builds up around the abdomen. About half of the participants received weekly injections of semaglutide, with the rest receiving placebo injections.
加州大学圣地亚哥分校及多家合作机构的研究人员分析了一项先前发表的临床试验数据，该试验涉及 108 名患有 HIV 相关脂肪增生症（一种腹部周围脂肪堆积过多的疾病）的成年人。约半数参与者每周接受一次司美格鲁肽注射，其余参与者则接受安慰剂注射。
The team used a set of biological “epigenetic clocks” to track cellular aging over the 32-week treatment period. These clocks detect DNA methylation, chemical marks on DNA that help regulate how genes are turned on or off without changing the genetic sequence itself. By measuring changes in these marks, the team could assess whether the treatment was associated with a slower or faster biological aging pattern.
研究团队使用了一套生物“表观遗传时钟”来追踪 32 周治疗期间的细胞衰老情况。这些时钟可以检测 DNA 甲基化，即 DNA 上的化学标记，它们在不改变基因序列本身的情况下帮助调节基因的开启或关闭。通过测量这些标记的变化，研究团队能够评估治疗是否与较慢或较快的生物衰老模式相关。
People with HIV often experience accelerated aging, even if it is well-controlled with antiretroviral therapy, according to first author Michael Corley, Ph.D., associate professor at UC San Diego School of Medicine and the Stein Institute for Research on Aging. However, the study found compared to the placebo group:
据第一作者、加州大学圣地亚哥分校医学院及斯坦衰老研究所副教授 Michael Corley 博士称，即使通过抗逆转录病毒疗法得到良好控制，HIV 感染者通常也会经历加速衰老。然而，该研究发现，与安慰剂组相比：
Participants treated with semaglutide exhibited a broad pattern of slower biological aging across epigenetic clocks linked to inflammation and blood, brain, heart, kidney, liver and metabolic health.
接受司美格鲁肽治疗的参与者在与炎症以及血液、大脑、心脏、肾脏、肝脏和代谢健康相关的表观遗传时钟上，表现出广泛的生物衰老减缓模式。
The drug slowed the pace of biological aging by 9 %, as measured by the DunedinPACE epigenetic clock.
根据 DunedinPACE 表观遗传时钟测量，该药物使生物衰老速度减缓了 9%。
The drug significantly slowed biological processes associated with the risk of all‑cause mortality and age-related disease, as measured by the PCGrimAge epigenetic clock.
根据 PCGrimAge 表观遗传时钟测量，该药物显著减缓了与全因死亡率和年龄相关疾病风险相关的生物过程。
Research suggests there are several mechanisms by which semaglutide may influence biological aging. By reducing inflammation and metabolic stress, GLP-1 drugs decreased chronic immune activation, a primary driver of accelerated aging in people with HIV. They also reduce visceral and ectopic fat that accumulates around the abdomen and organs, which may help curb the inflammatory and metabolic signals that promote aging.
研究表明，司美格鲁肽可能通过多种机制影响生物衰老。通过减少炎症和代谢压力，GLP-1 药物降低了慢性免疫激活，这是 HIV 感染者加速衰老的主要驱动因素。它们还减少了积聚在腹部和器官周围的内脏脂肪和异位脂肪，这可能有助于抑制促进衰老的炎症和代谢信号。
“Emerging data also suggest that GLP-1 drugs may reprogram certain cells in different organs, which could help explain why we see effects across multiple aging clocks,” said Corley.
Corley 表示：“新兴数据还表明，GLP-1 药物可能会重新编程不同器官中的某些细胞，这有助于解释为什么我们在多个衰老时钟中都观察到了效果。”
While the study focused on people with HIV‑associated lipohypertrophy, Corley says it may also offer lessons for the wider population.
虽然这项研究关注的是患有 HIV 相关脂肪增生症的人群，但 Corley 表示，它也可能为更广泛的人群提供借鉴。
“Many of the biological processes we study in HIV are also central to aging in the general population,” he said. “Because these processes can emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that may improve healthspan more broadly.”
他说：“我们在 HIV 研究中涉及的许多生物过程也是普通人群衰老的核心。由于这些过程在 HIV 感染者身上可能出现得更早或更明显，这一群体可以帮助我们确定可能更广泛地改善健康寿命的干预措施。”
In a related pilot study published in npj Aging last month, Corley and another team of researchers found that taking semaglutide for 24 weeks:
在上个月发表于《npj 衰老》（npj Aging）的一项相关试点研究中，Corley 和另一个研究团队发现，服用司美格鲁肽 24 周后：
Reduced the rate of biological aging for 42% of participants with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD) — also known as fatty liver disease — as measured by the DunedinPACE epigenetic clock. Those participants also had a greater reduction in liver fat compared with participants whose pace of aging sped up.
根据 DunedinPACE 表观遗传时钟测量，42% 患有 HIV 和代谢功能障碍相关脂肪性肝病（MASLD，也称为脂肪肝）的参与者的生物衰老速度有所降低。与衰老速度加快的参与者相比，这些参与者的肝脏脂肪减少幅度也更大。
Slowed aging associated with the risk of all‑cause mortality in 34% of participants as measured by the PCGrimAge epigenetic clock.
根据 PCGrimAge 表观遗传时钟测量，34% 的参与者与全因死亡率风险相关的衰老速度有所减缓。
Increased the length of telomeres — repetitive DNA sequences at the ends of chromosomes that protect genetic material — in nearly 49 % of participants as measured by the PCDNAmTL epigenetic clock. Those participants also tended to walk faster after treatment, suggesting better physical function.
根据 PCDNAmTL 表观遗传时钟测量，近 49% 的参与者的端粒（染色体末端保护遗传物质的重复 DNA 序列）长度增加。这些参与者在治疗后往往走得更快，表明身体机能有所改善。
Together, these studies add to growing evidence that GLP-1 drugs may influence pathways involved in biological aging.
总之，这些研究增加了越来越多的证据，表明 GLP-1 药物可能会影响参与生物衰老的途径。
“We are not saying that semaglutide reverses aging or makes people younger,” said Corley. “What we are seeing is a signal that it may slow some of the biological processes associated with aging. With newer GLP-1–based therapies now emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on aging biology and to identify which patients may benefit most.”
Corley 说：“我们并不是说司美格鲁肽能逆转衰老或让人变年轻。我们看到的是一个信号，表明它可能会减缓一些与衰老相关的生物过程。随着更新的基于 GLP-1 的疗法不断涌现，该领域有机会测试此类药物中不同的药物是否对衰老生物学有不同的影响，并确定哪些患者可能受益最大。”
Larger clinical trials are needed to confirm the findings, determine how long treatment effects last, and establish optimal dosing and treatment duration for both people with HIV and the broader population. Future studies will also be needed to test whether the effects of GLP-1 effects on aging biology are enhanced when combined with lifestyle interventions such as diet, exercise and sleep optimization.
需要更大规模的临床试验来证实这些发现，确定治疗效果的持续时间，并为 HIV 感染者和更广泛的人群确定最佳剂量和治疗持续时间。未来的研究还需要测试当 GLP-1 对衰老生物学的影响与饮食、运动和睡眠优化等生活方式干预相结合时，是否会得到增强。
The Stein Institute for Research on Aging plans to translate these results into individualized “aging dashboards” to track biological aging with epigenetic clocks, enabling clinicians to design personalized therapies that target the underlying mechanisms of aging and help prevent age‑related diseases.
斯坦衰老研究所计划将这些结果转化为个性化的“衰老仪表盘”，利用表观遗传时钟追踪生物衰老，使临床医生能够设计针对衰老潜在机制的个性化疗法，并帮助预防与年龄相关的疾病。
Additional co-authors on the Nature Communications study include: Alina P. S. Pang at UC San Diego; Varun Dwaraka and Ryan Smith at TruDiagnostic; Danielle Labbato and Grace A. McComsey at University Hospitals Cleveland Medical Center; Allison Ross Eckard at the Medical University of South Carolina; and Grace A. McComsey at Case Western Reserve University. The study was funded, in part, by the National Institutes of Health (grants P30 AI036214, R01DK121619 and UM1TR004528) and the James B. Pendleton Charitable Trust.
《自然-通讯》研究的其他共同作者包括：加州大学圣地亚哥分校的 Alina P. S. Pang；TruDiagnostic 的 Varun Dwaraka 和 Ryan Smith；克利夫兰大学医院医学中心的 Danielle Labbato 和 Grace A. McComsey；南卡罗来纳医科大学的 Allison Ross Eckard；以及凯斯西储大学的 Grace A. McComsey。该研究部分由美国国立卫生研究院（资助编号 P30 AI036214、R01DK121619 和 UM1TR004528）和 James B. Pendleton 慈善信托基金资助。
Additional co-authors on the npj Aging study include: Alina P. S. Pang at UC San Diego; Douglas W. Kitch and Amy Kantor at Harvard T.H. Chan School of Public Health; Fred Sattl
《npj 衰老》研究的其他共同作者包括：加州大学圣地亚哥分校的 Alina P. S. Pang；哈佛大学陈曾熙公共卫生学院的 Douglas W. Kitch 和 Amy Kantor；Fred Sattl。