Brittica guides

The 14 ageing switches: what calcium really does, and how Ca-AKG reaches more of them

You probably think of calcium as the bone mineral. It is, but that is only 99% of the story. The last 1% runs your heartbeat, your nerves, your muscles and the engines inside your cells. And when calcium is paired with alpha-ketoglutarate (AKG), it carries one of the most interesting molecules in ageing research: a molecule your body makes every second, and makes less of as the years go by.

This guide walks you through it in plain English. What calcium is, what it does, the different forms you see on supplement shelves, where Ca-AKG sits among them, the 14 ageing switches scientists now use to explain why we age (in the lab they are called the hallmarks of ageing), and which of those switches Ca-AKG+ can and cannot reach. We use reputable search engines and analytics software to see what people in the UK ask about this topic, and we built each section around those questions.

What is calcium?

Calcium is a mineral, element number 20, and the most abundant mineral in your body. An adult carries roughly a kilogram of it. Almost all of it is locked into hydroxyapatite, the hard crystal that gives bones and teeth their strength.^1,2

Your skeleton is not a static store. It is a living bank account. Every day, bone cells deposit and withdraw calcium, and your body moves calcium in and out of that account to keep the level in your blood steady.

What does calcium do in the body?

Here is the part most supplement labels skip. The 1% of calcium outside your bones is doing some of the most important jobs you have.

It keeps your blood level on a tight leash

Blood calcium is held between about 2.2 and 2.6 mmol/L. Three hormones manage it.² When blood calcium dips, the parathyroid glands release parathyroid hormone (PTH), which pulls calcium from bone and tells the kidneys to keep more. PTH also switches on calcitriol, the active form of vitamin D, which raises how much calcium you absorb from food. Calcitonin works the other way. This is why vitamin D matters so much: without it, you absorb only a fraction of the calcium you eat.

It is the signal that makes things move

Inside a resting cell, free calcium is kept around 10,000 times lower than outside. When a door opens and calcium floods in, the cell reacts.³ That spike makes muscle fibres contract, makes your heart beat, makes nerves release their messages, and makes hormone-secreting cells (including the beta cells that release insulin) let go of their cargo. Calcium is also a key factor in blood clotting.

It turns up the power in your mitochondria

This is the link to AKG. When calcium enters mitochondria, it activates three enzymes of energy metabolism: pyruvate dehydrogenase, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.⁴ In plain terms, calcium tells your cell’s power stations to work harder when demand rises. One of the molecules those enzymes process is AKG itself.

Too much calcium in the wrong place is a problem too. Calcium overload in mitochondria is one of the routes to cell damage, and calcium deposited in artery walls stiffens them. The goal is never “more calcium”. It is calcium in the right place.

Calcium deficiency: who is at risk?

The NHS sets the adult requirement at 700 mg a day and notes that most people get this from a varied diet including dairy, green leafy vegetables, tofu, fortified foods and fish with edible bones.⁵ People more likely to fall short include those who avoid dairy without replacing it, people with low vitamin D, older adults (absorption drops with age) and women after the menopause, when bone loss speeds up.

Long-term shortfalls show up slowly, mostly as thinning bones. Very low blood calcium is a different matter, usually linked to vitamin D, kidney or parathyroid problems rather than diet alone.

Forms of calcium supplements: carbonate, citrate and the rest

Walk down any supplement aisle and you meet a list of calcium salts. Each one pairs calcium with a different partner molecule, and that partner changes how much calcium you get and how well it is absorbed.⁶

Form	Calcium by weight	What to know
Calcium carbonate	About 40%	Cheapest and most concentrated. Needs stomach acid, so best taken with food. Can cause bloating or constipation.
Calcium citrate	About 21%	Absorbed with or without food, kinder to people with low stomach acid. Bigger tablets for the same dose.
Calcium lactate and gluconate	About 13% and 9%	Gentle but low in calcium, so you need a lot of them.
Calcium phosphate	About 38% (tribasic)	Common in fortified foods.
Calcium alpha-ketoglutarate (Ca-AKG)	A modest amount	Not a bone-calcium product. Here the partner molecule, AKG, is the reason to take it.

Calcium carbonate vs calcium citrate

If you want calcium for bones, carbonate gives you more per tablet and citrate is easier to absorb on an empty stomach. Both work best in doses of 500 mg or less at a time, because absorption falls as the dose rises.⁶

The calcium paradox, and why D3 and K2 matter

Large studies have raised a concern that high-dose calcium supplements, unlike calcium from food, may be linked to a small rise in heart attack risk.⁷ The debate continues, but it points to the same lesson: calcium needs to be steered into bone and kept out of arteries. Vitamin D3 helps you absorb it. Vitamin K2 activates osteocalcin, the protein that binds calcium straight into your bones and nowhere else.⁸ That is why Ca-AKG+ includes both.

What is Ca-AKG (calcium alpha-ketoglutarate)?

Ca-AKG is the calcium salt of alpha-ketoglutarate. Free AKG is an acid and not very stable on its own. Binding it to calcium makes a neutral, stable powder that is easy to put in a capsule. It is the form used in the landmark mouse study and in the current human trials.^10,13,14

So when you read “Ca-AKG”, think of the calcium as the delivery van and AKG as the parcel.

What does alpha-ketoglutarate do?

AKG is not a foreign compound. Your cells make it constantly. It has four big jobs.

1. Energy. AKG is a central stop on the Krebs cycle, the circular route inside mitochondria that turns food into usable energy.¹⁵
2. Nitrogen handling. It picks up and passes on nitrogen, linking it to glutamate and glutamine, which matter for muscle, the gut and the immune system.¹⁵
3. Collagen. The enzymes that make collagen strong (prolyl hydroxylases) need AKG and vitamin C to work.¹⁶
4. Gene control. The enzymes that remove chemical tags from DNA (TET enzymes) and from histones (JmjC demethylases) also need AKG. These are the enzymes that keep your genes switched on and off in the right pattern.¹⁶

Studies in mice and rats show that circulating AKG falls with age.¹¹ Less AKG means less fuel for all four jobs. That is the core idea behind supplementing it.

The 14 ageing switches (the hallmarks of ageing)

In 2013, a group of scientists led by Carlos López-Otín set out nine biological processes that drive ageing. They called them the hallmarks of ageing. In 2023 the list grew to twelve, and in April 2025 the same team added two more, bringing it to fourteen.^17,18,31 We call them ageing switches, because that is how they behave. Each one flips on as we get older. Pushing it further speeds up ageing in experiments, and turning it back down slows ageing. Here they are in plain English.

1. Genomic instability. DNA damage builds up faster than it is repaired.
2. Telomere attrition. The protective caps on chromosomes shorten each time a cell divides.
3. Epigenetic alterations. The tags that tell genes when to switch on and off drift out of pattern. This is what “biological age” clocks measure.¹⁹
4. Loss of proteostasis. Proteins misfold and clump, and quality control weakens.
5. Disabled macroautophagy. The cell’s recycling system slows, so damaged parts linger.
6. Deregulated nutrient sensing. Growth signals such as insulin, IGF-1 and mTOR stay switched on too much.
7. Mitochondrial dysfunction. Power stations make less energy and more oxidative waste.²⁰
8. Cellular senescence. Damaged cells stop dividing but refuse to die, and leak inflammatory signals.
9. Extracellular matrix changes. The scaffold of collagen and other proteins that holds your tissues together stiffens and loses its spring. New in 2025.³¹
10. Stem cell exhaustion. Repair cells run out of steam, so tissues renew more slowly.
11. Altered intercellular communication. Cells send and read signals less accurately.
12. Chronic inflammation. A low, constant hum of inflammation, sometimes called inflammaging.²¹
13. Dysbiosis. The balance of gut bacteria shifts.
14. Psychosocial isolation. Loneliness and shrinking social ties. Also new in 2025, and the researchers place it at the centre of their diagram, because long-term stress from isolation feeds into every other switch.³¹

None of these works alone. Like the organs behind type 2 diabetes, they feed each other: poor mitochondria raise inflammation, inflammation drives senescence, senescent cells exhaust stem cells. That network view is exactly why a single-ingredient fix rarely moves the needle far.

How AKG reaches the ageing switches

AKG is unusual because it touches several switches from one molecule. Here is what the research shows, switch by switch.

• Extracellular matrix (collagen). The newest switch on the list plays straight to AKG’s strengths. The enzymes that build strong, cross-linked collagen cannot work without AKG.¹⁶ In the 2025 update, the researchers describe a matrix that loses its spring with age and affects mitochondria, senescence and stem cells along the way.³¹
• Epigenetic alterations. The gene-tag-removing enzymes depend on AKG. In aged mice, AKG lowered repressive histone marks in bone stem cells and restored their bone-building signals.^11,16
• Stem cell exhaustion and senescence. In the same study, AKG reduced senescence in bone marrow stem cells and increased bone mass in old mice.¹¹ In embryonic stem cells, the balance of AKG helps decide whether cells stay flexible.²²
• Deregulated nutrient sensing and autophagy. In worms, AKG extended lifespan by gently slowing ATP synthase and dampening mTOR, the same growth pathway targeted by fasting and rapamycin.¹²
• Chronic inflammation. Ca-AKG lowered inflammatory cytokines in old mice and raised the anti-inflammatory signal IL-10 in females.¹⁰
• Mitochondrial dysfunction. AKG is Krebs cycle fuel, and its processing is directly switched on by calcium inside mitochondria.^4,15

What does the research on Ca-AKG show?

Here is the evidence in one table.

Study	Who	What happened
Chin et al., Nature 201412	Worms (C. elegans)	AKG extended lifespan by about 50%, through ATP synthase and mTOR.
Asadi Shahmirzadi et al., Cell Metabolism 202010	Mice, started at 18 months (roughly late middle age)	Ca-AKG cut frailty by 46% and stretched healthy lifespan by more than 40%. Average lifespan rose about 12%, mostly in females. Lower inflammation; males kept more muscle and fur, with less hunching.
Wang et al., Nature Communications 202011	Aged mice and rats	Blood AKG falls with age. AKG increased bone mass and reduced stem cell senescence.
Demidenko et al., Aging 202113	42 adults taking a Ca-AKG formula	Average biological age (DNA methylation clock) about 8 years lower after roughly 7 months.
ABLE trial (NCT05706389)14	120 adults aged 40 to 60	Double-blind, placebo-controlled: 1 g Ca-AKG daily for 6 months, measuring biological age. Results due.

Why we built Ca-AKG+ around more than AKG

Look at the diagram again. AKG alone reaches several switches, but ageing is a network. So we surrounded it with ingredients chosen for the gaps.

What is in two capsules of Ca-AKG+

Ingredient	Amount	Why it is there
Calcium alpha-ketoglutarate (99%)	1,000 mg	The same daily amount used in the ABLE trial.14
Ubiquinol CoQ10	120 mg	The active, ready-to-use form of CoQ10, the electron carrier in your mitochondria. Levels fall with age.23
PQQ	10 mg	Studied for helping cells build new mitochondria.24
Wheat germ extract (spermidine source)	5 mg	Spermidine switches on autophagy, the cell’s recycling system. Higher dietary spermidine is linked to longer life in population data.25,26
French pine bark extract (70% PCOs)	120 mg	Polyphenols studied for calming the NF-κB inflammation switch.27
Olive leaf extract (70% hydroxytyrosol)	50 mg	Hydroxytyrosol is studied for supporting mitochondrial renewal and antioxidant defences.28
Magnesium (glycinate)	125 mg	Contributes to normal energy-yielding metabolism and to the reduction of tiredness and fatigue.* Glycinate is a gentle, well absorbed form.29,30
Vitamin D3	25 µg (500% NRV)	Contributes to the maintenance of normal bones and muscle function.*
Vitamin K2 (MK-7)	100 µg (133% NRV)	Contributes to the maintenance of normal bones.* Activates the proteins that steer calcium into bone.8,9

Sixty size-00 plant capsules, a month’s supply. Take two with breakfast. Contains wheat.

Already taking GlycoShift? Choose one or the other rather than both. They share CoQ10 and PQQ, and together they would take PQQ above the 20 mg a day level set for food supplements. Supple X can be taken alongside either.

Ready to give your cells what they lose with age?

Every year you wait, the AKG in your blood keeps drifting down. Ninety days is enough to build the habit and see how you feel, which is why our most popular option is the 90-Day Vitality Routine.

Frequently asked questions

Is Ca-AKG a calcium supplement?

Not really. It contains calcium, but only as the stable carrier for AKG. If you need calcium for your bones, a dedicated calcium carbonate or citrate product with vitamin D is the better choice.

Does alpha-ketoglutarate reverse ageing?

Nobody can honestly say that yet. In mice, Ca-AKG reduced frailty and extended healthy lifespan. In people, an uncontrolled study saw biological age clocks fall, and a placebo-controlled trial is due to report. We will update this page when it does.

What is the difference between AKG and Ca-AKG?

AKG is the active molecule. Ca-AKG is AKG bound to calcium, which makes it stable and neutral. It is the form used in the key mouse study and in the human trials.

When is the best time to take Ca-AKG+?

Two capsules with breakfast. Taking it with food is easy on the stomach and helps fat-soluble ingredients such as ubiquinol, D3 and K2 absorb.

Can I take Ca-AKG+ with GlycoShift?

We recommend one at a time. Both contain CoQ10 and PQQ, and taking both would put your PQQ above the 20 mg a day level set for food supplements. Supple X can be taken alongside either.

Is AKG safe?

AKG is a normal product of your own metabolism and is found in small amounts in food. In the published studies, Ca-AKG was well tolerated. Ca-AKG+ contains wheat, so it is not suitable if you have a wheat allergy or coeliac disease.

How much calcium do I need a day?

The NHS recommends 700 mg a day for adults and says taking 1,500 mg a day or less in supplements is unlikely to cause harm.⁵

*Magnesium contributes to the reduction of tiredness and fatigue and to normal energy-yielding metabolism. Vitamin D contributes to the maintenance of normal bones and normal muscle function. Vitamin K contributes to the maintenance of normal bones. Food supplements should not replace a varied, balanced diet and a healthy lifestyle.

References

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32. Keyword research: reputable search engine and analytics data (Google Search UK; DataForSEO; OpenSEO), November 2026.

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