How Metformin Slows Aging
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Metformin And How It Slows Down Aging
That’s a bold claim for a title, but the scientific consensus is clear, and this Research Review Monday we’re going to take a look at exactly that!
Metformin is a common diabetes-management drug, used to lower blood sugar levels in people who either don’t have enough insulin or the insulin isn’t being recognized well enough by the body.
However, it also slows aging, which is a quality it’s also been studied for for more than a decade. We’ll look at some of the more recent research, though. Let’s kick off with an initial broad statement, from the paper “The Use of Metformin to Increase the Human Healthspan”, as part of the “Advances in Experimental Medicine and Biology” series:
In recent years, more attention has been paid to the possibility of using metformin as an anti-aging drug. It was shown to significantly increase the lifespan in some model organisms and delay the onset of age-associated declines. Growing amounts of evidence from clinical trials suggest that metformin can effectively reduce the risk of many age-related diseases and conditions, including cardiometabolic disorders, neurodegeneration, chronic inflammation and frailty.
How does it work?
That’s still being studied, but the scientific consensus is that it works by inducing hormesis—the process by which minor stress signals cells to start repairing themselves. How does it induce that hormesis? Again, still being studied, but it appears to do it by activating a specific enzyme; namely, the AMP-activated protein kinase:
Read: Metformin-enhances resilience via hormesis
It also has been found to slow aging by means of an anti-inflammatory effect, as a bonus!
Any bad news?
Well, firstly, in most places it’s only prescribed for diabetes management, not for healthy life extension. A lot of anti-aging enthusiasts have turned to the grey market online to get it, and we can’t recommend that.
Secondly, it does have some limitations:
- Its bioavailability isn’t great in tablet form (the form in which it is most commonly given)
- It has quite a short elimination half-life (around 6 hours), which makes it great to fix transient hyperglycemia in diabetics—job done and it’s out—but presents a logistical challenge when it comes to something so pernicious as aging.
- Some people are non-responders (a non-responder, in medicine, is someone for whom a drug simply doesn’t work, for no obvious reason)
Want to know more? Check out:
Metformin in aging and aging-related diseases: clinical applications and relevant mechanism
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How Aging Changes At 44 And Again At 60 (And What To Do About It)
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As it turns out, aging is not linear. Or rather: chronological aging may be, but biological aging isn’t, and there are parts of our life where it kicks into a different gear. This study looked at 108 people (65 of whom women) between the ages of 25 and 75, as part of a longitudinal cohort study, tracked for around 2–8 years (imprecise as not all follow-up durations were the same). They took frequent blood and urine samples, and tested them for thousands of different molecules and analyzing changes in gene expression, proteomic, blood biomarkers, and more. All things that are indicators of various kinds of health/disease, and which might seem more simple but it isn’t: aging.
Here’s what they found:
Landmark waypoints
At 44, significant changes occur in the metabolism, including notably the metabolism of carbs, caffeine, and alcohol. A large portion of this may be hormone related, as that’s a time of change not just for those undergoing the menopause, but also the andropause (not entirely analogous to the menopause, but it does usually entail a significant reduction in sex hormone production; in this case, testosterone).
However, the study authors also hypothesize that lifestyle factors may be relevant, as one’s 40s are often a stressful time, and an increase in alcohol consumption often occurs around the same time as one’s ability to metabolize it drops, resulting in further dysfunctional alcohol metabolism.
At 60, carb metabolism slows again, with big changes in glucose metabolism specifically, as well as an increased risk of cardiovascular disease, and a decline in kidney function. In case that wasn’t enough: also an increase free radical pathology, meaning a greatly increased risk of cancer. Immune function drops too.
What to do about this: the recommendation is of course to be proactive, and look after various aspects of your health before it becomes readily apparent that you need to. For example, good advice for anyone approaching 44 might be to quit alcohol, go easy on caffeine, and eat a diet that is conducive to good glucose metabolism. Similarly, good advice for anyone approaching 60 might be to do the same, and also pay close attention to keeping your kidneys healthy. Getting regular tests done is also key, including optional extras that your doctor might not suggest but you should ask for, such as blood urea nitrogen levels (biomarkers of kidney function). The more we look after each part of our body, the more they can look after us in turn, and the fewer/smaller problems we’ll have down the line.
If you, dear reader, are approaching the age 44 or 60… Be neither despondent nor complacent. We must avoid falling into the dual traps of “Well, that’s it, bad health is around the corner, nothing I can do about it; that’s nature”, vs “I’ll be fine, statistics are for other people, and don’t apply to me”.
Those are averages, and we do not have to be average. Every population has statistical outliers. But it would be hubris to think none of this will apply to us and we can just carry on regardless. So, for those of us who are approaching one of those two ages… It’s time to saddle up, knuckle down, and do our best!
For more on all of this, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
Also, if you’d like to read the actual paper by Dr. Xiaotao Shen et al., here it is:
Nonlinear dynamics of multi-omics profiles during human aging ← honestly, it’s a lot clearer and more informative than the video, and also obviously discusses things in a lot more detail than we have room to here
Take care!
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Montana Eyes $30M Revamp of Mental Health, Developmental Disability Facilities
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HELENA, Mont. — As part of a proposed revamping of the state’s behavioral health system, Republican Gov. Greg Gianforte’s administration is looking into moving a facility for people with developmental disabilities, beefing up renovations at the Montana State Hospital, and creating a Helena unit of that psychiatric hospital.
The changes, backers say, would fill gaps in services and help people better prepare for life outside of the locked, secure setting of the two state facilities before they reenter their own communities.
“I think part of the theme is responsibly moving people in and out of the state facilities so that we create capacity and have people in the appropriate places,” state Sen. Dave Fern (D-Whitefish) said of the proposed capital projects during a recent interview.
Fern served on the Behavioral Health System for Future Generations Commission, a panel created by a 2023 law to suggest how to spend $300 million to revamp the system. The law set aside the $300 million for improving state services for people with mental illness, substance abuse disorders, and developmental disabilities.
Gianforte’s proposed budget for the next two years would spend about $100 million of that fund on 10 other recommendations from the commission. The capital projects are separate ideas for using up to $32.5 million of the $75 million earmarked within the $300 million pool of funds for building new infrastructure or remodeling existing buildings.
The state Department of Public Health and Human Services and consultants for the behavioral health commission presented commission members with areas for capital investments in October. In December, the commission authorized state health department director Charlie Brereton to recommend the following projects to Gianforte:
- Move the 12-bed Intensive Behavior Center for people with developmental disabilities out of Boulder, possibly to either Helena or Butte, at an estimated cost of up to $13.3 million.
- Establish a “step-down” facility of about 16 beds, possibly on the campus of Shodair Children’s Hospital in Helena, to serve adults who have been committed to the Montana State Hospital but no longer need the hospital’s intensive psychiatric services.
- Invest $19.2 million to upgrade the Montana State Hospital’s infrastructure and buildings at Warm Springs, on top of nearly $16 million appropriated in 2023 for renovations already underway there in an effort to regain federal certification of the facility.
The state Architecture & Engineering Division is reviewing the health department’s cost estimates and developing a timeline for the projects so the information can be sent to the governor. Gianforte ultimately must approve the projects.
Health department officials have said they plan to take the proposals to legislative committees as needed. “With Commission recommendation and approval from the governor, the Department believes that it has the authority to proceed with capital project expenditures but must secure additional authority from the Legislature to fund operations into future biennia,” said department spokesperson Jon Ebelt.
The department outlined its facility plans to the legislature’s health and human services budget subcommittee on Jan. 22 as part of a larger presentation on the commission’s work and the 10 noncapital proposals in the governor’s budget. Time limits prevented in-depth discussion and public comment on the facility-related ideas.
One change the commission didn’t consider: moving the Montana State Hospital to a more populated area from its rural and relatively remote location near Anaconda, in southwestern Montana, in an attempt to alleviate staffing shortages.
“The administration is committed to continuing to invest in MSH as it exists today,” Brereton told the commission in October, referring to the Montana State Hospital.
The hospital provides treatment to people with mental illness who have been committed to the state’s custody through a civil or criminal proceeding. It’s been beset by problems, including the loss of federal Medicaid and Medicare funding due to decertification by the federal government in April 2022, staffing issues that have led to high use of expensive traveling health care providers, and turnover in leadership.
State Sen. Chris Pope (D-Bozeman) was vice chair of a separate committee that met between the 2023 and 2025 legislative sessions and monitored progress toward a 2023 legislative mandate to transition patients with dementia out of the state hospital. He agreed in a recent interview that improving — not moving — MSH is a top priority for the system right now.
“Right now, we have an institution that is failing and needs to be brought back into the modern age, where it is located right now,” he said after ticking off a list of challenges facing the hospital.
State Sen. John Esp (R-Big Timber) also noted at the October commission meeting that moving the hospital was likely to run into resistance in any community considered for a new facility.
Fern, the Whitefish senator, questioned in October whether similar concerns might exist for moving the Intensive Behavior Center out of Boulder. For more than 130 years, the town 30 miles south of Helena has been home, in one form or another, to a state facility for people with developmental disabilities. But Brereton said he believes relocation could succeed with community and stakeholder involvement.
The 12-bed center in Boulder serves people who have been committed by a court because their behaviors pose an immediate risk of serious harm to themselves or others. It’s the last residential building for people with developmental disabilities on the campus of the former Montana Developmental Center, which the legislature voted in 2015 to close.
Drew Smith, a consultant with the firm Alvarez & Marsal, told the commission in October that moving the facility from the town of 1,300 to a bigger city such as Helena or Butte would provide access to a larger labor pool, possibly allow a more homelike setting for residents, and open more opportunities for residents to interact with the community and develop skills for returning to their own communities.
Ideally, Brereton said, the center would be colocated with a new facility included in the governor’s proposed budget, for crisis stabilization services to people with developmental disabilities who are experiencing significant behavioral health issues.
Meanwhile, the proposed subacute facility with up to 16 beds for state hospital patients would provide a still secure but less structured setting for people who no longer need intensive treatment at Warm Springs but aren’t yet ready to be discharged from the hospital’s care. Brereton told the commission in October the facility would essentially serve as a less restrictive “extension” of the state hospital. He also said the agency would like to contract with a company to staff the subacute facility.
Health department officials don’t expect the new facility to involve any construction costs. Brereton has said the agency believes an existing building on the Shodair campus would be a good spot for it.
The state began leasing the building Nov. 1 for use by about 20 state hospital patients displaced by the current remodeling at Warm Springs — a different purpose than the proposed subacute facility.
Shodair CEO Craig Aasved said Shodair hasn’t committed to having the state permanently use the building as the step-down facility envisioned by the agency and the commission.
But Brereton said the option is attractive to the health department now that the building has been set up and licensed to serve adults.
“It seems like a natural place to start,” he told the commission in December, “and we don’t mind that it’s in our backyard here in Helena.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Subscribe to KFF Health News’ free Morning Briefing.
This article first appeared on KFF Health News and is republished here under a Creative Commons license.
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Carbonated Water: For Weight Loss, Satiety, Or Just Gas?
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There are two main mechanisms of action by which sparkling water is considered to help satiety and/or weight loss; they are:
- It “fills us up” such that we feel fuller sooner, and thus eat less, and thus (all other things being equal) perhaps lose weight
- The carbon dioxide is absorbed into the bloodstream, where (as a matter of chemistry) it improves glucose metabolism, thus lowering blood sugars and indirectly leading (potentially) to weight loss, but even if not, lowered blood sugars are good for most people most of the time, right?
However, there are just a few problems:
Full of gas?
Many people self-report enjoying sparkling water as a way to feel fuller while fasting (or even while eating). However, the plural of “anecdote” is not “data”, so, here be data… Ish:
❝In order to determine whether such satiating effects occur through oral carbonic stimulation alone, we conducted modified sham-feeding (SF) tests (carbonated water ingestion (CW), water ingestion (W), carbonated water sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent volume and standardized temperature of carbonated and plain water, in a randomized crossover design.
Thirteen young women began fasting at 10 p.m. on the previous night and were loaded with each sample (15ºC, 250 mL) at 9 a.m. on separate days. Electrogastrography (EGG) recordings were obtained from 20 min before to 45 min after the loading to determine the power and frequency of the gastric myoelectrical activity. Appetite was assessed using visual analog scales. After ingestion, significantly increased fullness and decreased hunger ratings were observed in the CW group. After the load, transiently but significantly increased fullness as well as decreased hunger ratings were observed in the CW-SF group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed significant increases in the CW and W groups, but not in the CW-SF and W-SF groups. The peak frequency of normogastria tended to shift toward a higher band in the CW group, whereas it shifted toward a lower band in the CW-SF group, indicating a different EGG rhythm.
Our results suggest that CO2-induced oral stimulation is solely responsible for the feeling of satiety.❞
~ Dr. Maki Suzuki et al.
Now, that’s self-reported, and a sample size of 13, so it’s not the most airtight science ever, but it is at least science. Here’s the paper, by the way:
Oral Carbonation Attenuates Feeling of Hunger and Gastric Myoelectrical Activity in Young Women
Here’s another small study with 8 people, which found that still and sparkling water had the exact same effect:
Effect of carbonated water on gastric emptying and intragastric meal distribution
However, drinking water (still or sparkling) with a meal will not have anywhere near the same effect for satiety as consuming food that has a high water-content.
See also: Some Surprising Truths About Hunger And Satiety ← our main feature in which we examine the science of volumetrics, including a study that shows how water incorporated into a food (but not served with a food) decreases caloric intake.
As an aside, one difference that carbonation can make is to increase ghrelin levels—that’s the hunger hormone (the satiety hormone is leptin, by the way). This one’s a rat study, but it seems reasonable that the same will be true of humans:
…which is worth bearing in mind even if you yourself are not, in fact, a male rat.
The glucose guzzler?
This one has simply been the case of a study being misrepresented, for example here:
Fizzy water might aid weight loss by providing a small boost to glucose uptake and metabolism
The idea is that higher levels of carbon dioxide in the blood mean faster glucose metabolism, which is technically true. Now, often “technically true” is the best kind of true, but not here, because it’s simply not useful.
In short, we produce so much carbon dioxide as part of our normal respiratory processes, that any carbon dioxide we might consume in a carbonated water is barely a blip in the graph.
Oh, and that article we just linked? Even within the article, despite running with that headline, the actual scientists quoted are saying such things as:
❝While there is a hypothetical link between carbonated water and glucose metabolism, this has yet to be tested in well-designed human intervention studies❞
~ Professor Sumantra Ray
Note: the word “hypothetical” means “one level lower than theoretical”. This is very far from being a conclusion.
And the study itself? Wasn’t even about carbonated water, it was about kidney dialysis and how the carbon dioxide content can result in hypoglycemia:
The mechanism of hypoglycemia caused by hemodialysis
…which got referenced in this paper (not a study):
Can carbonated water support weight loss?
…and even that concluded:
❝CO2 in carbonated water may promote weight loss by enhancing glucose uptake and metabolism in red blood cells.
However, the amount is so small that it is difficult to expect weight loss effects solely from the CO2 in carbonated water.
Drinking carbonated water may also affect blood glucose measurements.❞
Note: the word “may”, when used by a scientist and in the absence of any stronger claims, means “we haven’t ruled out the possibility”.
What breaking news that is.
Stop the press! No, really, stop it!
So… What does work?
There are various ways of going about actually hacking hunger (and they stack; i.e. you can use multiple methods and get cumulative results), and we wrote about them here:
Enjoy!
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Ozempic’s cousin drug liraglutide is about to get cheaper. But how does it stack up?
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Fourteen years ago, the older drug cousin of semaglutide (Ozempic and Wegovy) came onto the market. The drug, liraglutide, is sold under the brand names Victoza and Saxenda.
Patents for Victoza and Saxenda have now expried. So other drug companies are working to develop “generic” versions. These are likely be a fraction of current cost, which is around A$400 a month.
So how does liraglutide compare with semaglutide?
Halfpoint/Shutterstock How do these drugs work?
Liraglutide was not originally developed as a weight-loss treatment. Like semaglutide (Ozempic), it originally treated type 2 diabetes.
The class of drugs liraglutide and semaglutide belong to are known as GLP-1 mimetics, meaning they mimic the natural hormone GLP-1. This hormone is released from your small intestines in response to food and acts in several ways to improve the way your body handles glucose (sugar).
How do they stop hunger?
Liraglutide acts in several regions of the unconscious part of your brain, specifically the hypothalamus, which controls metabolism, and parts of the brain stem responsible for communicating your body’s nutrient status to the hypothalamus.
Its actions here appear to reduce hunger in two different ways. First, it helps you to feel full earlier, making smaller meals more satisfying. Second, it alters your “motivational salience” towards food, meaning it reduces the amount of food you seek out.
Liraglutide’s original formulation, designed to treat type 2 diabetes, was marketed as Victoza. Its ability to cause weight loss was evident soon after it entered the market.
Shortly after, a stronger formulation, called Saxenda, was released, which was intended for weight loss in people with obesity.
How much weight can you lose with liraglutide?
People respond differently and will lose different amounts of weight. But here, we’ll note the average weight loss users can expect. Some will lose more (sometimes much more), others will lose less, and a small proportion won’t respond.
The first GLP-1 mimicking drug was exenatide (Bayetta). It’s still available for treating type 2 diabetes, but there are currently no generics. Exenatide does provide some weight loss, but this is quite modest, typically around 3-5% of body weight.
For liraglutide, those using the drug to treat obesity will use the stronger one (Saxenda), which typically gives about 10% weight loss.
Semaglutide, with the stronger formulation called Wegovy, typically results in 15% weight loss.
The newest GLP-1 mimicking drug on the market, tirzepatide (Mounjaro for type 2 diabetes and Zepbound for weight loss), results in weight loss of around 25% of body weight.
What happens when you stop taking them?
Despite the effectiveness of these medications in helping with weight loss, they do not appear to change people’s weight set-point.
So in many cases, when people stop taking them, they experience a rebound toward their original weight.
People often regain weight when when they stop taking the drug. Mohammed_Al_Ali/Shutterstock What is the dose and how often do you need to take it?
Liraglutide (Victoza) for type 2 diabetes is exactly the same drug as Saxenda for weight loss, but Saxenda is a higher dose.
Although the target for each formulation is the same (the GLP-1 receptor), for glucose control in type 2 diabetes, liraglutide has to (mainly) reach the pancreas.
But to achieve weight loss, it has to reach parts of the brain. This means crossing the blood-brain barrier – and not all of it makes it, meaning more has to be taken.
All the current formulations of GLP-1 mimicking drug are injectables. This won’t change when liraglutide generics hit the market.
However, they differ in how frequently they need to be injected. Liraglutide is a once-daily injection, whereas semaglutide and tirzepatide are once-weekly. (That makes semaglutide and tirzepatide much more attractive, but we won’t see semaglutide as a generic until 2033.)
What are the side effects?
Because all these medicines have the same target in the body, they mostly have the same side effects.
The most common are a range of gastrointestinal upsets including nausea, vomiting, bloating, constipation and diarrhoea. These occur, in part, because these medications slow the movement of food out of the stomach, but are generally managed by increasing the dose slowly.
Recent clinical data suggests the slowing in emptying of the stomach can be problematic for some people, and may increase the risk of of food entering the lungs during operations, so it is important to let your doctor know if you are taking any of these drugs.
Because these are injectables, they can also lead to injection-site reactions.
Gastrointestinal side effects are most common. Halfpoint/Shutterstock During clinical trials, there were some reports of thyroid disease and pancreatitis (inflammation of the pancreas). However, it is not clear that these can be attributed to GLP-1 mimicking drugs.
In animals, GLP-1 mimicking drugs drugs have been found to negatively alter the growth of the embryo. There is currently no controlled clinical trial data on their use during pregnancy, but based on animal data, these medicines should not be used during pregnancy.
Who can use them?
The GLP-1 mimicking drugs for weight loss (Wegovy, Saxenda, Zepbound/Mounjaro) are approved for use by people with obesity and are meant to only be used in conjunction with diet and exercise.
These drugs must be prescribed by a doctor and for obesity are not covered by the Pharmaceutical Benefits Scheme, which is one of the reasons why they are expensive. But in time, generic versions of liraglutide are likely to be more affordable.
Sebastian Furness, ARC Future Fellow, School of Biomedical Sciences, The University of Queensland
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Steps vs Cardio | Which is Best for Fat Loss, Health, & Performance?
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“Move more”, they say; but does it matter how quickly?
Use it or lose it
For general performance:
- More steps per day do offer slight aerobic benefits but do not significantly improve endurance.
- Higher-intensity cardio (ideally, HIIT) is essential for improving aerobic fitness.
- Training should match endurance goals (e.g. long-distance running vs team sports vs whatever it is that you care about for you).
For general health:
- Both cardio and step tracking reduce mortality risk and improve longevity.
- 2–3 hours of cardio per week provides most health benefits, with diminishing returns after 8 hours per week.
- 10,000+ steps/day is optimal, but 5,000+ steps/day still benefits health. And, not mentioned in this video, but really (per science) there seem to be diminishing returns after about 8,000 steps per day.
Fun fact: the reason it’s 10,000 steps per day that everyone talks about as the default goal, is just because the Japanese person who popularized it noted that the kanji for 10,000 looks a bit like a walking person: 万
For fat loss:
- Both step tracking and cardio do help.
- Step tracking better reflects total daily movement, while cardio burns calories in sessions—but if it’s not HIIT, there is likely to be a compensatory metabolic slump afterwards.
- High-intensity cardio increases fatigue, which may impact resistance training and diet adherence.
- Excessive endurance training can slightly inhibit muscle growth, but low-intensity steps have minimal interference.
So for fat loss, it’s best to get those steps in, and throw in a few HIIT sessions per week, with adequate recovery time between them.
For more on all of these things, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
How To Do HIIT (Without Wrecking Your Body)
Take care!
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Top Foods Against Neuroinflammation
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Chronic inflammation is something you might feel in your joints, but it will usually be in the brain too. There, neuroinflammation can disrupt brain function, affecting stress responses, mood, cognition, and even alter brain structure. It’s also heavily implicated in the pathogenesis of various forms of dementia.
What to do about it
Dr. Tracey Marks, psychiatrist, bids us eat:
- Fatty fish: omega-3-rich fish like salmon reduce neuroinflammation.
- Leafy greens: spinach, kale, and collards protect brain cells and support neurotransmitter production.
- Berries: blueberries and strawberries improve memory and protect neurons.
- Nuts and seeds: walnuts, almonds, and flaxseeds support brain health and reduce inflammation.
- Turmeric: curcumin combats inflammation and supports neuron growth (best with supplements).
- Fermented foods: yogurt and sauerkraut improve gut health, benefiting the brain via the gut-brain axis; not just the vagus nerve, but also, remember that various neurotransmitters (including serotonin) are made in the gut.
Of course, you should also avoid alcohol, nicotine, red meat, processed meat, and ideally also white flour products, and sugary foods (unless they are also rich in fiber, like whole fruit).
For more on each of these, enjoy:
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Want to learn more?
You might also like to read:
How to Prevent (or Reduce) Inflammation
Take care!
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