{"id":1364,"date":"2025-08-17T13:53:33","date_gmt":"2025-08-17T13:53:33","guid":{"rendered":"https:\/\/scienceblog.com\/joshmitteldorf\/?p=1364"},"modified":"2025-08-18T16:49:42","modified_gmt":"2025-08-18T16:49:42","slug":"review-of-anti-aging-drugs","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2025\/08\/17\/review-of-anti-aging-drugs\/","title":{"rendered":"Review of Anti-Aging Drugs"},"content":{"rendered":"

 <\/p>\n

Since 2017<\/span><\/a>, the <\/span>DrugAge database<\/span><\/a> has been a resource cataloguing longevity studies for many substances fed to animals in lab experiments. A <\/span>preprint<\/span><\/a> by Parish et al was recently posted to the bioRxiv website which assessed the quality of these various studies and sought to draw conclusions.<\/span><\/p>\n

Parish et al include a table of drugs (including supplements) that have been tested for life extension in different model animals. One of the first conclusions they draw is that the correlation between what works in mammals and what works in simple animals is very low (r=0.28, not statistically significant). Of course, it is much cheaper and more convenient to work with worms or flies instead of mice, but the chances are that our experience there will not carry over to mammals like us.\u00a0<\/span><\/p>\n

Taking this to heart, I have ignored the part of the table devoted to invertebrates, and sorted the results according to average lifespan increase in mice or rats. The second column tells us how many experiments have been reported and (in parenthesis) the total number of animals averaged from all these experiments.\u00a0<\/span><\/p>\n

All reported life extensions in mammals are modest, with the best achieving 10-20% increase. (In contrast, much longer percentage increases are available for shorter-lived fruitflies and lab worms.) Here\u2019s my perspective: Aging is the result of an evolved adaptive program, each animal regulating its own lifespan in response to perceived environment. Lifespan is under the body\u2019s control, with a flexible response in the range of <\/span>+\/-<\/span>20%. My interpretation of lifespan extension technologies in the DrugAge is that they all work within the inherent flexibility of the program, tricking the body into thinking that circumstances justify lifespan toward the higher end. In mice we might get 10-20% enhancement with this model, but in humans the corresponding flexibility is more limited, and we can expect 10 extra years at the outside. 10 extra years is, of course, well worth the effort. But I believe there are larger potential benefits from hacking (defeating) the signaling system to go beyond the programmed range of flexibility. This is why I\u2019m so enthusiastic about <\/span>exosome therapies<\/span><\/a>.\u00a0\u00a0<\/span><\/p>\n

(If you have no patience for the details, jump ahead to a brief summary at the end.)<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Compound<\/b><\/td>\n# Mammal Experiments (Total N)<\/b><\/td>\n# Nonmammal Experiments (Total N)<\/b><\/td>\nMammal SMD (p)<\/b><\/td>\nNonmammal SMD (p)<\/b><\/td>\nMammal % Increase in Lifespan<\/b><\/td>\nNonmammal % Increase in Lifespan<\/b><\/td>\n<\/tr>\n
Ascorbic<\/span><\/td>\n1 (24)<\/span><\/td>\n3 (404)<\/span><\/td>\n0.94 (0.038)<\/span><\/td>\n0.03 (0.91)<\/span><\/td>\n19.60%<\/span><\/td>\n2.00%<\/span><\/td>\n<\/tr>\n
Simvastatin<\/span><\/td>\n1 (682)<\/span><\/td>\n1 (400)<\/span><\/td>\n0.3 (0.0001)<\/span><\/td>\n0.69 (<0.0001)<\/span><\/td>\n19.00%<\/span><\/td>\n12.60%<\/span><\/td>\n<\/tr>\n
Royal jelly<\/span><\/td>\n1 (22)<\/span><\/td>\n4 (2308)<\/span><\/td>\n0.84 (0.060)<\/span><\/td>\n0.48 (0.0041)<\/span><\/td>\n17.90%<\/span><\/td>\n14.10%<\/span><\/td>\n<\/tr>\n
Skulachev quinone (SKQ)<\/span><\/td>\n1 (50)<\/span><\/td>\n1 (850)<\/span><\/td>\n0.86 (0.0038)<\/span><\/td>\n0.27 (0.0001)<\/span><\/td>\n15.10%<\/span><\/td>\n8.00%<\/span><\/td>\n<\/tr>\n
Epithalamin<\/span><\/td>\n2 (171)<\/span><\/td>\n2 (812)<\/span><\/td>\n0.85 (0.0047)<\/span><\/td>\n0.23 (0.0009)<\/span><\/td>\n14.90%<\/span><\/td>\n5.70%<\/span><\/td>\n<\/tr>\n
Taurine<\/span><\/td>\n1 (122)<\/span><\/td>\n1 (470)<\/span><\/td>\n0.8 (<0.0001)<\/span><\/td>\n0.6 (<0.0001)<\/span><\/td>\n14.50%<\/span><\/td>\n20.40%<\/span><\/td>\n<\/tr>\n
Calcium pantothenate<\/span><\/td>\n1 (74)<\/span><\/td>\n1 (197)<\/span><\/td>\n0.47 (0.047)<\/span><\/td>\n0.56 (0.0001)<\/span><\/td>\n12.60%<\/span><\/td>\n5.30%<\/span><\/td>\n<\/tr>\n
Vitamin E<\/span><\/td>\n1 (47)<\/span><\/td>\n10 (1621)<\/span><\/td>\n0.57 (0.055)<\/span><\/td>\n2.2 (0.17)<\/span><\/td>\n12.50%<\/span><\/td>\n6.50%<\/span><\/td>\n<\/tr>\n
N-acetylcysteine<\/span><\/td>\n1 (32)<\/span><\/td>\n8 (4006)<\/span><\/td>\n1.02 (0.0068)<\/span><\/td>\n0.55 (0.0003)<\/span><\/td>\n12.30%<\/span><\/td>\n15.30%<\/span><\/td>\n<\/tr>\n
Phenformin<\/span><\/td>\n1 (54)<\/span><\/td>\n1 (594)<\/span><\/td>\n0.6 (0.033)<\/span><\/td>\n0.27 (0.0011)<\/span><\/td>\n11.60%<\/span><\/td>\n28.50%<\/span><\/td>\n<\/tr>\n
Berberine<\/span><\/td>\n1 (44)<\/span><\/td>\n1 (360)<\/span><\/td>\n0.91 (0.004)<\/span><\/td>\n0.06 (0.58)<\/span><\/td>\n11.40%<\/span><\/td>\n4.60%<\/span><\/td>\n<\/tr>\n
Estradiol<\/span><\/td>\n1 (370)<\/span><\/td>\n1 (124)<\/span><\/td>\n0.33 (0.0021)<\/span><\/td>\n0.7 (0.0002)<\/span><\/td>\n11.30%<\/span><\/td>\n17.80%<\/span><\/td>\n<\/tr>\n
Epigallocatechin gallate<\/span><\/td>\n1 (60)<\/span><\/td>\n7 (1692)<\/span><\/td>\n0.52 (0.047)<\/span><\/td>\n0.35 (<0.0001)<\/span><\/td>\n11.20%<\/span><\/td>\n16.90%<\/span><\/td>\n<\/tr>\n
Melatonin<\/span><\/td>\n3 (160)<\/span><\/td>\n3 (344)<\/span><\/td>\n1.07 (0.0041)<\/span><\/td>\n0.83 (0.013)<\/span><\/td>\n11%<\/span><\/td>\n16.30%<\/span><\/td>\n<\/tr>\n
Magnesium lthiazolidine carboxylate<\/span><\/td>\n1 (75)<\/span><\/td>\n1 (331)<\/span><\/td>\n0.45 (0.053)<\/span><\/td>\n0.69 (<0.0001)<\/span><\/td>\n9.10%<\/span><\/td>\n21.40%<\/span><\/td>\n<\/tr>\n
Spermidine<\/span><\/td>\n4 (360)<\/span><\/td>\n3 (600)<\/span><\/td>\n0.56 (0.0004)<\/span><\/td>\n0.38 (<0.0001)<\/span><\/td>\n9.00%<\/span><\/td>\n22.00%<\/span><\/td>\n<\/tr>\n
Rapamycin<\/span><\/td>\n12 (2100)<\/span><\/td>\n6 (1919)<\/span><\/td>\n0.33 (0.0052)<\/span><\/td>\n1.84 (0.11)<\/span><\/td>\n7.90%<\/span><\/td>\n21.90%<\/span><\/td>\n<\/tr>\n
Curcumin<\/span><\/td>\n3 (293)<\/span><\/td>\n8 (3869)<\/span><\/td>\n0.45 (0.001)<\/span><\/td>\n0.42 (0.004)<\/span><\/td>\n7.20%<\/span><\/td>\n8.40%<\/span><\/td>\n<\/tr>\n
Alpha-keto glutarate<\/span><\/td>\n1 (44)<\/span><\/td>\n4 (769)<\/span><\/td>\n0.83 (0.0088)<\/span><\/td>\n0.49 (<0.0001)<\/span><\/td>\n6.80%<\/span><\/td>\n20.00%<\/span><\/td>\n<\/tr>\n
Icariin<\/span><\/td>\n1 (101)<\/span><\/td>\n1 (321)<\/span><\/td>\n0.25 (0.21)<\/span><\/td>\n0.43 (0.0001)<\/span><\/td>\n6.80%<\/span><\/td>\n28.90%<\/span><\/td>\n<\/tr>\n
Dinitrophenol<\/span><\/td>\n1 (60)<\/span><\/td>\n1 (40)<\/span><\/td>\n0.54 (0.042)<\/span><\/td>\n0.81 (0.014)<\/span><\/td>\n6.20%<\/span><\/td>\n7.90%<\/span><\/td>\n<\/tr>\n
Nordihydroguaiaretic<\/span><\/td>\n2 (455)<\/span><\/td>\n3 (480)<\/span><\/td>\n0.30 (0.37)<\/span><\/td>\n0.58 (<0.0001)<\/span><\/td>\n5.80%<\/span><\/td>\n25.80%<\/span><\/td>\n<\/tr>\n
D-glucosamine<\/span><\/td>\n1 (146)<\/span><\/td>\n1 (848)<\/span><\/td>\n0.51 (0.0024)<\/span><\/td>\n1.59 (<0.0001)<\/span><\/td>\n5.50%<\/span><\/td>\n2.70%<\/span><\/td>\n<\/tr>\n
Oxaloacetate<\/span><\/td>\n1 (310)<\/span><\/td>\n1 (144)<\/span><\/td>\n0.11 (0.32)<\/span><\/td>\n0.42 (0.013)<\/span><\/td>\n4.00%<\/span><\/td>\n20.00%<\/span><\/td>\n<\/tr>\n
Nicotinamide<\/span><\/td>\n3 (370)<\/span><\/td>\n3 (1365)<\/span><\/td>\n0.25 (0.083)<\/span><\/td>\n1.99 (0.24)<\/span><\/td>\n3.10%<\/span><\/td>\n19.40%<\/span><\/td>\n<\/tr>\n
Metformin<\/span><\/td>\n5 (519)<\/span><\/td>\n8 (3088)<\/span><\/td>\n0.06 (0.80)<\/span><\/td>\n0.42 (<0.0001)<\/span><\/td>\n3.00%<\/span><\/td>\n18.50%<\/span><\/td>\n<\/tr>\n
Aspirin<\/span><\/td>\n3 (471)<\/span><\/td>\n4 (880)<\/span><\/td>\n0.07 (0.50)<\/span><\/td>\n0.65 (0.017)<\/span><\/td>\n1.00%<\/span><\/td>\n16.20%<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Ascorbic acid (vitamin C)<\/span><\/h2>\n

In Parish\u2019s table, this ranks first with just one study and an average over 24 animals of 19.6% life extension. The study was by Massie (<\/span>1984<\/span><\/a>), and it reports 8% average increase. I don\u2019t know where the figure 19.6% comes from, and the article is behind Karger’s paywall.<\/span><\/p>\n

Simvastatin<\/span><\/h2>\n

Simvastatin is a statin drug (Merck, patent expired), and (disclaimer) I\u2019ve long been <\/span>suspicious of statins<\/span><\/a>. The single quoted study (Miller, <\/span>2011<\/span><\/a>) was by scientists I trust at Jackson Labs, who should have had no conflict of interest. The focus of the study was rapamycin \u2014 not simvastatin \u2014 but simvastatin was used as one of several controls. As far as I can see, the study did not report any increase in lifespan from simvastatin. I don\u2019t know where the 19% in the table comes from.<\/span><\/p>\n

Royal jelly<\/span><\/h2>\n

This is the mix of compounds that worker bees generate and feed to their queen. Queen bees live for up to 20 years, while workers (with the same genome) die after just a few weeks. There is one study (Inoue <\/span>2003<\/span><\/a>) in the DrugAge database feeding royal jelly to mice, and yes, at higher dosages, 15 mice lived an average 25% longer. As you can see below, early mortality was greatly reduced, but maximum lifespan wasn\u2019t affected.<\/span><\/p>\n

RJ is a natural antibiotic, and it is possible that the suppression of early mortality derives from prevention of infection. It is also possible that RJ selectively favors good bacteria in the gut. <\/span>Here is a study<\/span><\/a> in which RJ increased neural health and cognitive performance in aging rats. I would think that RJ deserves <\/span>more study<\/span><\/a>. <\/span><\/p>\n

\"\"<\/p>\n

SkQ<\/span><\/h2>\n

Half a century ago, the late great Vladimir Skulachev modified the CoQ10 molecule to a form that would be attracted into mitochondria, where it is most needed. Later, his and similar molecules were studied by Michael Murphy and Robin Smith in New Zealand for life extension benefits. Today, there are products from <\/span>Russia<\/span><\/a> and from <\/span>NZ<\/span><\/a> with similar forms of mitochondrial-targeted quinones. (The Russians are based on plant-derived plastiquinone, which they say is a more powerful antioxidant than CoQ10.)<\/span><\/p>\n

I can\u2019t find SkQ in the DrugAge database. But there are <\/span>several mouse studies<\/span><\/a> out of Vladimir Anisimov\u2019s St Petersburg laboratory. In <\/span>this one<\/span><\/a>, SkQ increased lifespan of outbred mice (closer to wild type), but not the inbred laboratory strain. I would like to see Western labs replicateand expand on the promising Russian studies.<\/span><\/p>\n

Epithalamin<\/span><\/h2>\n

Peptides are short proteins, in this case just 4 amino acids. Epithalamin is one of the peptides developed and tested by (again) Anisimov\u2019s lab group. \u201cEpithalamin\u201d refers to the \u201cdirty\u201d set of peptides derived from the pineal gland, among which the 4-amino-acid peptide called epitalon is assumed to be the active ingredient. But in the DrugAge database, epithalamin is a super-star, with 15% life extension, and epitalon is a loser, with no average life extension whatever (in rodents). This is curious.<\/span><\/p>\n

In the DrugAge database, there is one study each, both from Anisimov et al, for <\/span>eiptalon<\/span><\/a> and <\/span>epithalamin<\/span><\/a>.\u00a0 The negative result for epitalon is well-documented and new. The positive result for epithalamin is based on re-evaluation of poorly-documented studies from the past, 1979-92. This is disappointing.<\/span><\/p>\n

Taurine<\/span><\/h2>\n

Taurine is an amino acid, but it is not one of the 20 amino acids that are linked together to make proteins. It is non-essential, meaning that our bodies can synthesize it even if we don\u2019t have any in our diet. \u201cNevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body.\u201d [<\/span>ref<\/span><\/a>] The same reference argues that taurine is broadly neuroprotective, especially in the eye. Fun fact: it can protect you from Chinese Restaurant Syndrome(msg). Taurine levels in human blood decline with age, but increase in response to exercise \u2014 generally signs that more might be helpful.\u00a0<\/span><\/p>\n

There is one study in DrugAge (Singh, <\/span>2023<\/span><\/a>). \u201cMechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging.\u201d Mouse lifespan increased about 10% (Parish says 14% \u2014 I don\u2019t know where that comes from.)\"\"<\/span><\/p>\n

I hadn\u2019t been aware of the promise of taurine until reading this. I\u2019m going to add taurine to my supplement stack, and eagerly await more experimental results. Note that the dosage in the mouse experiments is quite high \u2014 0.1% of the body weight every day, meaning about 2 ounces a day for me (70 kg). It doesn\u2019t have much taste, so can be added to smoothies. Two ounces is too much to take in pill form.\u00a0<\/span><\/p>\n

Calcium pantothenate<\/span><\/h2>\n

Pantothenic acid is a B vitamin (B5). DrugAge has <\/span>one study<\/span><\/a> from 1958 that has never been repeated, because pantothenate is thought to be in good supply in the normal human diet. The 1958 study reported a 20% lifespan increase in mice, however the lifespans of control mice was suspiciously short.<\/span><\/p>\n

Vitamin E<\/span><\/h2>\n

The DrugAge database refers to the <\/span>same Sohal study<\/span><\/a> referenced above. In the original paper, there is no lifespan increase for supplementation with vitamins A, C, or E. I don\u2019t know why <\/span>Parish<\/span><\/a> reports a 12% increase.<\/span><\/p>\n

N-Acetylcysteine (NAC)<\/span><\/h2>\n

This is a precursor to glutathione, and the most accessible way to boost glutathione levels. I\u2019m prejudiced because I\u2019ve already touted NAC as <\/span>my favorite <\/span><\/a>supplement<\/span><\/a>, In DrugAge, I found a single study from some of my favorite people at Jackson Labs (<\/span>2010<\/span><\/a>). Not mentioned was a <\/span>more recent study<\/span><\/a> in which NAC was given in conjunction with glycine (an amino acid), and which showed a large LS benefit. \"\"<\/span><\/p>\n

The graph below is from the Jackson Lab study. The males enjoyed a whopping 20-30% lifespan increase, depending how you measure it. The female controls were living longer, and the NAC didn\u2019t add significantly to their LS. \"\"<\/span><\/p>\n

I think there is plenty of evidence now to justify life extension enthusiasts taking NAC, possibly in conjunction with glycine. But more studies would be most welcome.<\/span><\/p>\n

Metformin \/ Phenformin \/ Berberine<\/span><\/h2>\n

Metformin is tried-and-true anti-diabetic drug which incidentally lowers risk of cancer and dementia. It has been a natural go-to for life extension enthusiasts. Phenformin is a higher powered version, but regulatory agencies have declared it too dangerous for use in humans because of risk of lactic acidosis. Berberine is a herbal supplement which offers similar benefits to metformin or phenformin, but without the side effects. Metformin has been studied a great deal more than either berberine or phenformin.<\/span><\/p>\n

In the DrugAge database,\u00a0<\/span><\/p>\n