Since 2017, the DrugAge database has been a useful resource cataloguing longevity research for a lot of substances fed to animals in lab experiments. A preprint by Parish et al was not too long ago posted to the bioRxiv web site which assessed the standard of those varied research and sought to attract conclusions.
Parish et al embody a desk of medicine (together with dietary supplements) which were examined for all times extension in numerous mannequin animals. One of many first conclusions they draw is that the correlation between what works in mammals and what works in easy animals could be very low (r=0.28, not statistically vital). After all, it’s less expensive and extra handy to work with worms or flies as a substitute of mice, however the chances are high that our expertise there is not going to carry over to mammals like us.
Taking this to coronary heart, I’ve ignored the a part of the desk dedicated to invertebrates, and sorted the outcomes in line with common lifespan improve in mice or rats. The second column tells us what number of experiments have been reported and (in parenthesis) the entire variety of animals averaged from all these experiments.
All reported life extensions in mammals are modest, with one of the best attaining 10-20% improve. (In distinction, for much longer proportion will increase can be found for shorter-lived fruitflies and lab worms.) Right here’s my perspective: Getting older is the results of an developed adaptive program, every animal regulating its personal lifespan in response to perceived setting. Lifespan is below the physique’s management, with a versatile response within the vary of +/-20%. My interpretation of lifespan extension applied sciences within the DrugAge is that all of them work throughout the inherent flexibility of this system, tricking the physique into pondering that circumstances justify lifespan towards the upper finish. In mice we’d get 10-20% enhancement with this mannequin, however in people the corresponding flexibility is extra restricted, and we are able to count on 10 further years on the exterior. 10 further years is, in fact, nicely definitely worth the effort. However I imagine there are bigger potential advantages from hacking (defeating) the signaling system to transcend the programmed vary of flexibility. Because of this I’m so passionate about exosome therapies.
(You probably have no persistence for the main points, leap forward to a quick abstract on the finish.)
| Compound | # Mammal Experiments (Whole N) | # Nonmammal Experiments (Whole N) | Mammal SMD (p) | Nonmammal SMD (p) | Mammal % Enhance in Lifespan | Nonmammal % Enhance in Lifespan |
| Ascorbic | 1 (24) | 3 (404) | 0.94 (0.038) | 0.03 (0.91) | 19.60% | 2.00% |
| Simvastatin | 1 (682) | 1 (400) | 0.3 (0.0001) | 0.69 (<0.0001) | 19.00% | 12.60% |
| Royal jelly | 1 (22) | 4 (2308) | 0.84 (0.060) | 0.48 (0.0041) | 17.90% | 14.10% |
| Skulachev quinone (SKQ) | 1 (50) | 1 (850) | 0.86 (0.0038) | 0.27 (0.0001) | 15.10% | 8.00% |
| Epithalamin | 2 (171) | 2 (812) | 0.85 (0.0047) | 0.23 (0.0009) | 14.90% | 5.70% |
| Taurine | 1 (122) | 1 (470) | 0.8 (<0.0001) | 0.6 (<0.0001) | 14.50% | 20.40% |
| Calcium pantothenate | 1 (74) | 1 (197) | 0.47 (0.047) | 0.56 (0.0001) | 12.60% | 5.30% |
| Vitamin E | 1 (47) | 10 (1621) | 0.57 (0.055) | 2.2 (0.17) | 12.50% | 6.50% |
| N-acetylcysteine | 1 (32) | 8 (4006) | 1.02 (0.0068) | 0.55 (0.0003) | 12.30% | 15.30% |
| Phenformin | 1 (54) | 1 (594) | 0.6 (0.033) | 0.27 (0.0011) | 11.60% | 28.50% |
| Berberine | 1 (44) | 1 (360) | 0.91 (0.004) | 0.06 (0.58) | 11.40% | 4.60% |
| Estradiol | 1 (370) | 1 (124) | 0.33 (0.0021) | 0.7 (0.0002) | 11.30% | 17.80% |
| Epigallocatechin gallate | 1 (60) | 7 (1692) | 0.52 (0.047) | 0.35 (<0.0001) | 11.20% | 16.90% |
| Melatonin | 3 (160) | 3 (344) | 1.07 (0.0041) | 0.83 (0.013) | 11% | 16.30% |
| Magnesium lthiazolidine carboxylate | 1 (75) | 1 (331) | 0.45 (0.053) | 0.69 (<0.0001) | 9.10% | 21.40% |
| Spermidine | 4 (360) | 3 (600) | 0.56 (0.0004) | 0.38 (<0.0001) | 9.00% | 22.00% |
| Rapamycin | 12 (2100) | 6 (1919) | 0.33 (0.0052) | 1.84 (0.11) | 7.90% | 21.90% |
| Curcumin | 3 (293) | 8 (3869) | 0.45 (0.001) | 0.42 (0.004) | 7.20% | 8.40% |
| Alpha-keto glutarate | 1 (44) | 4 (769) | 0.83 (0.0088) | 0.49 (<0.0001) | 6.80% | 20.00% |
| Icariin | 1 (101) | 1 (321) | 0.25 (0.21) | 0.43 (0.0001) | 6.80% | 28.90% |
| Dinitrophenol | 1 (60) | 1 (40) | 0.54 (0.042) | 0.81 (0.014) | 6.20% | 7.90% |
| Nordihydroguaiaretic | 2 (455) | 3 (480) | 0.30 (0.37) | 0.58 (<0.0001) | 5.80% | 25.80% |
| D-glucosamine | 1 (146) | 1 (848) | 0.51 (0.0024) | 1.59 (<0.0001) | 5.50% | 2.70% |
| Oxaloacetate | 1 (310) | 1 (144) | 0.11 (0.32) | 0.42 (0.013) | 4.00% | 20.00% |
| Nicotinamide | 3 (370) | 3 (1365) | 0.25 (0.083) | 1.99 (0.24) | 3.10% | 19.40% |
| Metformin | 5 (519) | 8 (3088) | 0.06 (0.80) | 0.42 (<0.0001) | 3.00% | 18.50% |
| Aspirin | 3 (471) | 4 (880) | 0.07 (0.50) | 0.65 (0.017) | 1.00% | 16.20% |
Ascorbic acid (vitamin C)
In Parish’s desk, this ranks first with only one examine and a median over 24 animals of 19.6% life extension. The examine was by Sohal (1985), and it reviews on a number of totally different dosages in a number of animal species. I don’t know the place the determine 19.6% comes from, however the conclusion of this examine was that supplementation with vitamin C depressed lifespan, in all probability by inhibiting manufacturing of the physique’s native antioxidants, together with glutathione and SOD=superoxide dismutase.
Simvastatin
Simvastatin is a statin drug (Merck, patent expired), and (disclaimer) I’ve lengthy been suspicious of statins. The one quoted examine (Miller, 2011) was by scientists I belief at Jackson Labs, who ought to have had no battle of curiosity. The main target of the examine was rapamycin — not simvastatin — however simvastatin was used as one among a number of controls. So far as I can see, the examine didn’t report any improve in lifespan from simvastatin. I don’t know the place the 19% within the desk comes from.
Royal jelly
That is the combination of compounds that employee bees generate and feed to their queen. Queen bees stay for as much as 20 years, whereas staff (with the identical genome) die after just some weeks. There’s one examine (Inoue 2003) within the DrugAge database feeding royal jelly to mice, and sure, at increased dosages, 15 mice lived a median 25% longer. As you may see under, early mortality was significantly diminished, however most lifespan wasn’t affected.
RJ is a pure antibiotic, and it’s potential that the suppression of early mortality derives from prevention of an infection. Additionally it is potential that RJ selectively favors good micro organism within the intestine. Here’s a examine through which RJ elevated neural well being and cognitive efficiency in growing older rats. I’d suppose that RJ deserves extra examine.
SkQ
Half a century in the past, the late nice Vladimir Skulachev modified the CoQ10 molecule to a kind that might be attracted into mitochondria, the place it’s most wanted. Later, his and related molecules have been studied by Michael Murphy and Robin Smith in New Zealand for all times extension advantages. As we speak, there are merchandise from Russia and from NZ with related types of mitochondrial-targeted quinones. (The Russians are based mostly on plant-derived plastiquinone, which they are saying is a extra highly effective antioxidant than CoQ10.)
I can’t discover SkQ within the DrugAge database. However there are a number of mouse research out of Vladimir Anisimov’s St Petersburg laboratory. In this one, SkQ elevated lifespan of outbred mice (nearer to wild sort), however not the inbred laboratory pressure. I want to see Western labs replicateand broaden on the promising Russian research.
Epithalamin
Peptides are quick proteins, on this case simply 4 amino acids. Epithalamin is among the peptides developed and examined by (once more) Anisimov’s lab group. “Epithalamin” refers back to the “soiled” set of peptides derived from the pineal gland, amongst which the 4-amino-acid peptide known as epitalon is assumed to be the energetic ingredient. However within the DrugAge database, epithalamin is a super-star, with 15% life extension, and epitalon is a loser, with no common life extension no matter (in rodents). That is curious.
Within the DrugAge database, there’s one examine every, each from Anisimov et al, for eiptalon and epithalamin. The adverse outcome for epitalon is well-documented and new. The optimistic outcome for epithalamin relies on re-evaluation of poorly-documented research from the previous, 1979-92. That is disappointing.
Taurine
Taurine is an amino acid, however it isn’t one of many 20 amino acids which might be linked collectively to make proteins. It’s non-essential, that means that our our bodies can synthesize it even when we don’t have any in our food plan. “Nonetheless, contemplating its broad distribution, its many cytoprotective attributes, and its practical significance in cell improvement, diet, and survival, taurine is undoubtedly one of the important substances within the physique.” [ref] The identical reference argues that taurine is broadly neuroprotective, particularly within the eye. Enjoyable truth: it may well shield you from Chinese language Restaurant Syndrome(msg). Taurine ranges in human blood decline with age, however improve in response to train — usually indicators that extra could be useful.
There’s one examine in DrugAge (Singh, 2023). “Mechanistically, taurine diminished mobile senescence, protected in opposition to telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA injury, and attenuated inflammaging.” Mouse lifespan elevated about 10% (Parish says 14% — I don’t know the place that comes from.)
I hadn’t been conscious of the promise of taurine till studying this. I’m going so as to add taurine to my complement stack, and eagerly await extra experimental outcomes. Word that the dosage within the mouse experiments is kind of excessive — 0.1% of the physique weight every single day, that means about 2 ounces a day for me (70 kg). It doesn’t have a lot style, so might be added to smoothies. Two ounces is an excessive amount of to soak up tablet kind.
Calcium pantothenate
Pantothenic acid is a B vitamin (B5). DrugAge has one examine from 1958 that has by no means been repeated, as a result of pantothenate is regarded as in good provide within the regular human food plan. The 1958 examine reported a 20% lifespan improve in mice, nevertheless the lifespans of management mice was suspiciously quick.
Vitamin E
The DrugAge database refers back to the similar Sohal examine referenced above. Within the unique paper, there isn’t a lifespan improve for supplementation with nutritional vitamins A, C, or E. I don’t know why Parish reviews a 12% improve.
N-Acetylcysteine (NAC)
It is a precursor to glutathione, and essentially the most accessible method to increase glutathione ranges. I’m prejudiced as a result of I’ve already touted NAC as my favourite complement, In DrugAge, I discovered a single examine from a few of my favourite folks at Jackson Labs (2010). Not talked about was a newer examine through which NAC was given together with glycine (an amino acid), and which confirmed a big LS profit. 
The graph under is from the Jackson Lab examine. The males loved a whopping 20-30% lifespan improve, relying the way you measure it. The feminine controls have been dwelling longer, and the NAC didn’t add considerably to their LS. 
I believe there’s loads of proof now to justify life extension lovers taking NAC, probably together with glycine. However extra research could be most welcome.
Metformin / Phenformin / Berberine
Metformin is tried-and-true anti-diabetic drug which by the way lowers danger of most cancers and dementia. It has been a pure go-to for all times extension lovers. Phenformin is a better powered model, however regulatory businesses have declared it too harmful to be used in people due to danger of lactic acidosis. Berberine is a natural complement which presents related advantages to metformin or phenformin, however with out the unwanted side effects. Metformin has been studied an excellent deal greater than both berberine or phenformin.
Within the DrugAge database,
Within the Sturdy examine (2016) a mix of metformin and rapamycin achieved one of the best outcomes. You’ll be able to see that median lifespan elevated about 20%, imply LS considerably much less, and max LS under no circumstances. The modest enchancment in LS from this mixture is sobering, since
- Metformin and rapamycin are arguably the 2 compounds for which there’s essentially the most strong proof for all times extension in rodents, and
- There are theoretical and experimental causes to imagine that the mixture synergizes to supply higher outcomes than both compound individually.
I’ve written up to now that combos of remedies are an enormous, unexplored territory from which new outcomes ought to be sought. In observe, folks in search of life extension virtually all the time take a mix of dietary supplements, interactions amongst that are utterly unknown.
17α-Hydroxyestrone
It is a steroid hormone akin to estrogen. There are 4 research within the DrugAge database feeding 16α-Hydroxyestrone to mice. 12-19% LS will increase for male LS are reported, however for females the outcomes or null or, typically, adverse. The outcomes come from authors I belief at Jackson Labs.
Epicatechin within the kind Epigallocatechin gallate
Epicatechin is a flavinoid derived from chocolate. One of many happiest leads to epidemiology is that individuals who eat chocolate stay longer. In a single Chinese language examine of EGCG, lifespan of rats elevated 14%. (The desk in Parish says 11%.)
Melatonin
Dr Walter Pierpaoli has been a lifelong advocate for melatonin, together with in style books and lab analysis. Melatonin is popularly generally known as the pineal hormone that regulates sleep/wake cycles; however melatonin can be important to mitochondrial perform, and there’s much more melatonin in our mitochondria than in our bloodstreams. The DrugAge database lists simply two research, Pierpaoli (1994) discovered a 17% improve in mouse LS and Anisimov (2001) discovered a 7% improve and warned of a rise in tumor frequency.
The Pierpaoli experiment timed the melatonin to circadian rhythms, and Anisimov didn’t.
Magnesium
Magnesium is listed within the Parish desk with a 9% LS profit in mammals, however I used to be unable to search out rodent research in DrugAge involving magnesium. Searches in PubMed and Google Scholar additionally turned up no mouse LS research of magnesium. (I take magnesium dietary supplements myself for management of blood sugar and prevention of muscle cramps.)
Spermidine
Spermidine is a straightforward molecule with advantages as anti-inflammatory and pro-autophagy. I wrote about spermidine final 12 months. There are two spermidine mouse research within the DrugAge database, Yue (2017) and Eisenberg (2016)
Spermidine supplementation supplied modest life extension advantages even when began late in life, however dosage was giant in comparison with complement capsules which might be generally obtainable.
Rapamycin
After a Jackson Lab examine discovered spectacular LS enchancment for rapa fed to mice late in life, (Harrison, 2009), there was a substantial amount of enthusiasm for a brand new longevity pathway. Sixteen years later, there are 12 rodent research in DrugAge — greater than every other substance — however outcomes are much less spectacular. Parish computes a median of 8% lifespan improve, which places rapa far down his sorted listing. That is an artifact of averaging excessive and low dosages, pulsed and regular, late and early administration. I personally imagine rapa is extra promising than the 8% would point out.
The best dosage corresponded to 26% LS improve within the most optimistic examine, additionally out of Jackson Labs. Individuals who take a look at the detailed biochemistry distinguish between Rapa-1 and Rapa-2, and recommend pulsing the dosage in people. Personally, I take giant doses of rapamycin 2 days per week, 8 weeks per 12 months. For customized suggestions, you may seek the advice of your favourite life extension doc.
Curcumin, fish oil, Boswellia and aspirin
I group these collectively as a result of they’re all anti-inflammatory brokers. I imagine that countering power irritation is essentially the most strong method to lengthen human lifespan.
There have been two rodent research in Drugage that are listed below “curcumin”. Katani (2007) discovered 10% LS improve in mice. The opposite was Knoll (2016), and actually it’s about deprenyl and BPAP, not associated to curcumin.
Miller (2019) discovered no profit from aspirin. Sturdy (2008) discovered a small profit for male mice. 
Fish oil isn’t within the Parish chart, however is in two DrugAge research. Spindler (2014) discovered that fish oil and krill oil shortened mouse LS. Sturdy (2016) reported no profit. I’d qualify these outcomes by noting that mouse lipid metabolism could also be totally different from that of people in vital methods. Boswellia is neither in Parish nor in DrugAge, however it’s a protected and historical anti-inflammatory herb.
Alpha Ketoglutarate (AKG)
Within the Parish chart, AKG is related to a 7% longevity profit. There are two research in DrugAge. Shahmirzadi (2020) reported a modest profit in females greater than males.
Miller (2024) report no profit for AKG.
Creatine
Creatine is in style amongst body-builders, and Rhonda Patrick has been passionate about advantages recently. It’s omitted of the Parish database, however it’s in DrugAge, and Bender (2007) reviews an 8% LS profit in mice.
Glucosamine
Glucosamine can be omitted in Parish, however there are entries in DrugAge that present some promise. Weimer (2014) reviews modest LS profit for glucosamine administered late within the mouse lifetime.
Deprenyl (Selegiline)
Deprenyl is among the oldest life extension interventions (Knoll, 1968), however it isn’t within the Parish listing. It’s bought as a psychiatric drug below the names selegiline, eldepryl, emsam, and zelepar. In DrugAge, there are 4 rat research and one mouse examine, additionally one canine examine.
The canine examine discovered a survival profit for canines began on deprenyl late in life. Archer (1997) reported 6 to 9% improve in LS for mice when began late in life. Kitani (2005) reported 8% improve in rats, additionally begun late in life. Milgram (1990) reported a 17% LS profit in rats. I don’t perceive why deprenyl was excluded from the Parish examine.
Losers
Each different in style complement, together with CoQ10, Alpha Lipoic Acid (ALA), NMN, NR, DHEA and Quercetin, had no impact on lifespan, or worse.
Abstract
My favorites from this listing are Melatonin, Berberine, NAC, Rapamycin, and Selegiline. I can suggest the primary three unequivocally. Rapamycin has down sides that you must contemplate, and Selegiline has results on temper and power that you could be like or dislike. Personally, I take quite a lot of anti-inflammatory dietary supplements, and I’m glad to have an excuse to eat darkish chocolate. I don’t know why there have been no mouse research of vitamin D. There are broad advantages from vitamin D, and I’d be stunned if they didn’t embody life extension.
All these medicine and dietary supplements act throughout the built-in plasticity of the growing older program, which is about 20% in rodents, however solely 5 – 10% in people. It’s unlikely that we are able to stack the dietary supplements and count on quite a lot of further years of lifespan for our effort. The perfect purpose to take a number of life extension dietary supplements is to hedge our bets, as a result of we actually don’t know which ones are efficient in people.
Your main life extension program is food plan and train. Select a food plan that works for you. Keep slim. Quick for brief intervals frequently, and longer fasts as they really feel good to you. Select quite a lot of bodily actions which might be self-motivating and embody interval coaching, power coaching, flexibility, stability, and endurance. Dietary supplements and medicines are secondary.
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