Time flies! It feels like 2024 just started, and yet 2025 is already around the corner. A quick question: how’s your anti-aging journey going? Looking back at 2024, the field of anti-aging substances has seen intense competition—veteran anti-aging "heavyweights" remain strong, while new contenders have emerged like shining stars...
Do you have a favorite anti-aging substance? At this critical juncture of the year transition, we’ve carefully compiled the "2024 Annual Anti-Aging Substances Ranking List". Who made the cut? After following anti-aging substances for a whole year, this list offers a clear overview—you won’t want to miss it!
Part 1: Annual Best Duo – 40% Lifespan Extension, Proving "1+1>2"
When it comes to golden pairs for combined anti-aging, the DQ combo (Dasatinib + Quercetin), known for clearing senescent cells, is no stranger. But this year, a new pair has gained fame for its lifespan-extending effects: Dendrobium officinale and Spermidine—deserving of the title "Annual Best Anti-Aging Duo".
The combination of high-dose Dendrobium officinale polysaccharides (250 mg/L) and high-dose Spermidine (29 mg/L) (dubbed the DS-HH combo) was found to extend the median lifespan of nematodes by 40%. It also enhanced the nematodes’ resistance to oxidative stress and heat stress, improved motor ability, and showed remarkable effects in reducing lipid accumulation and alleviating metabolic impairment.
Figure Notes: Effects of different doses of Dendrobium officinale polysaccharides combined with Spermidine on nematode lifespan (Group A and Group B show survival rates over days for different combinations vs. control group).
Dendrobium officinale is a "divine herb" recorded in Shennong's Classic of Materia Medica (an ancient Chinese medical text) for its ability to "lighten the body and prolong life". Spermidine, meanwhile, is a rising star in anti-aging research in recent years. The combination of this traditional Chinese medicine and a new anti-aging substance miraculously achieves a "1+1>2" anti-aging effect! When a single anti-aging substance can’t meet practical needs, trying a mix of traditional and new ingredients may be the way to go.
Part 2: Most Talked-About of the Year – Even "Aphrodisiacs" Can Fight Aging?
If Dendrobium officinale works well in combination for anti-aging, another traditional Chinese medicine—Epimedium (Horny Goat Weed)—has something to say: "Don’t think I can only boost libido; I’m good at anti-aging too!"
Epimedium’s ability to enhance libido and improve sexual dysfunction has long been documented in ancient Chinese medical classics, earning it the title "the predecessor of Viagra". But don’t underestimate this herb: its main active component, Icariin, can extend nematode lifespan by nearly 90%, reduce lipid droplet accumulation, relieve inflammation, and improve muscle and ovarian aging—comprehensively enhancing both lifespan and healthspan!
Figure Notes: Purple lines represent nematodes in three experimental groups given different concentrations of Icariin; gray lines represent the control group (no Icariin). N2 = wild-type nematodes; daf-2 = nematodes with the daf-2 gene knocked out.
Studies have found that Icariin extends nematode lifespan through the daf-2 pathway, which corresponds to the insulin/IGF-1 pathway in humans. Thus, Icariin—known for boosting human libido—may also hold the key to extending human lifespan!
Moreover, the safety and efficacy of Icariin have already been partially verified in human clinical trials for cancer treatment. Whether it will become a future star in anti-aging may just be a matter of time.
Part 3: Annual Most Promising Clinical Newcomer – Among "Elixirs of Youth", Some Thrive, Some Struggle
Clinical trials are the ultimate test of an anti-aging substance’s effectiveness—some fail miserably, while others forge ahead steadily. NR (Nicotinamide Riboside), one of the NAD+ precursors, is among the steadfast pioneers. Although its "fellow companion" NMN has been banned for sale in some regions due to various reasons, NR remains at the forefront of anti-aging research.
In the second half of this year, ChromaDex—a biotech company focused on healthy aging—launched its latest product, "intravenous NR (NR IV)", and conducted the first human clinical trial of injectable NR. Results showed that the NR injection group exhibited excellent safety, efficacy (NAD+ levels increased by 20.7% from baseline), and tolerability, with only mild adverse reactions—marking a preliminary success in human trials.
Figure Note: Blood NAD+ levels measured at different time points (Baseline, 10 min, 3 hr, 6 hr, 24 hr, 7 day, 14 day) for groups receiving NAD+ IV, NR IV, Saline (control), and Oral NR.
Since all participants were healthy individuals over 40, further clinical trials are needed to determine whether intravenous NR can improve age-related diseases or symptoms. However, Charles Brenner—Chief Scientific Advisor of the company and the discoverer of NR’s efficacy—seems confident about future progress.
Figure Note: Professor Charles Brenner
Part 4: Annual Most Popular – Mushrooms Step Out of Market Corners
Down-to-earth anti-aging fruits and vegetables emerge every year, but mushrooms stand out the most in 2024. Why has this ordinary ingredient gained such attention? It all comes down to its active component: Ergothioneine!
Ergothioneine is a sulfur-containing amino acid with powerful antioxidant and anti-inflammatory properties. It has been found to extend lifespan (by 6%-12% in nematodes and 21% in mice) while alleviating age-related frailty (e.g., weight loss, movement disorders). It also works wonders in improving cognition and slowing cellular aging!
Figure Notes: a) Oral Ergothioneine extends mouse lifespan and non-frail period; b) & c) Survival rates of mice in control group vs. groups given 5 mM/10 mM Ergothioneine over days.
Despite its great benefits, the human body cannot produce Ergothioneine on its own—it must be obtained from external food sources. Professor Barry Halliwell, an authority on the free radical theory and researcher at the National University of Singapore, advises: "Eat more mushrooms." Don’t like mushrooms? Liver, kidneys, black beans, red beans, and oat bran are also good alternative sources!
Part 5: Annual Dark Horse – Standing on the Shoulders of Giants, Surpassing Predecessors
No discussion of trending anti-aging substances would be complete without Akkermansia muciniphila—a gut bacterium isolated from human feces that has gained huge popularity in recent years. This year, it sent a capable "protégé" to the list: the Amuc_1100 protein.
Extracted from the outer membrane of Akkermansia muciniphila, this protein embodies most of the bacterium’s anti-aging and health benefits, such as fighting inflammation, maintaining intestinal homeostasis, improving metabolism, regulating immunity, and enhancing brain cognition. Remarkably, compared to Akkermansia muciniphila itself, Amuc_1100 can withstand high temperatures (up to 70°C) and requires a much lower dosage—making it far more applicable.
Figure Notes: Effects of Amuc_1100 on intestinal barrier protection and damage repair: a) Relative expression levels of tight junction proteins (red) and occludin (green) (Amuc_1100 group vs. PBS control); b) Serum LPS levels (a marker of intestinal permeability); c) Relative diameter of colonic organoids; d) Number of rectal organoids (Day 3/5/7, control vs. experimental group).
Fecal microbiota transplantation (FMT) is currently one of the anti-aging methods to address the age-related decline in Akkermansia muciniphila levels. While extending lifespan is hard enough, "eating feces to live longer" is simply unpalatable for most people. With Amuc_1100, however, not only is the "hard-to-swallow" problem solved, but the effect may also be better—isn’t that much more acceptable?
Part 6: Annual Most Unique – Trametinib: "This Time, I Choose Females!"
Did you know there’s a "male bias" in the anti-aging field? Many anti-aging drugs tested in the U.S. official Interventions Testing Program (ITP) only extend the lifespan of males, with no effect on females. But this year, Trametinib—a dual-purpose drug for cancer and anti-aging—made the list for its "female-biased" lifespan-extending trait.
Trametinib was found to reduce the activity of RNA polymerase III (Pol III) throughout the body, in the intestines, and in intestinal stem cells (elevated Pol III activity negatively impacts stem cell function, intestinal health, and animal survival). This improves age-related intestinal pathology and extends the lifespan of female fruit flies.
Figure Note: Survival curves of fruit flies (DMSO control vs. Trametinib group) – Trametinib extends the lifespan of female fruit flies but has no significant effect on males.
Furthermore, studies have shown that Trametinib’s lifespan-extending mechanism (via Pol III inhibition) is similar to that of rapamycin—an established anti-aging drug also known for its "female bias". When combined, the two can extend the lifespan of female mice by 35%.
Part 7: Annual Most Regrettable – "Schrödinger’s NMN": Both "Dead" and "Alive"
Some anti-aging substances make the list for thriving in anti-aging research, while others are included due to their rocky journey—case in point: NMN (Nicotinamide Mononucleotide).
In late May this year, rumors circulated that China’s General Administration of Customs would impose a comprehensive ban on NMN starting in June. Multiple domestic e-commerce platforms also received notices stating that NMN products could no longer be sold via cross-border e-commerce channels from June 1, sparking widespread concern in the industry. Although no official document has been released yet, NMN’s status in China remains uncertain.
In contrast, NMN—long restricted in some regions—seems to have caught a break overseas. It was reported that the U.S. FDA announced it would not restrict NMN sales until July 31, 2025, during which it will issue an updated ruling on NMN’s regulatory status. This provides a temporary grace period for NMN’s legal sales in the U.S., but its long-term fate remains unpredictable.
Figure Note: "Why Did the FDA Ban NMN?" (explanatory graphic on NMN’s regulatory status)
Regardless of NMN’s regulatory twists and turns, the scientific community continues to pay close attention to NMN research (there have been numerous studies on NMN this year). Perhaps the problem lies not with NMN itself, but with NMN supplements driven by commercial interests. Caught between favorable and unfavorable circumstances, NMN’s future may only be revealed by ongoing scientific progress.
Part 8: Final Showstopper – Annual Most Watched: This "Metformin" Leaves Us Wanting More
Friends, it’s time for the most exciting moment! Please welcome the finalist, top-ranked, and most discussed anti-aging substance of the year (applause)!
- For over 60 years since its launch, it has been widely praised as an anti-diabetic drug for its safety, affordability, and efficacy.
- It has been proven to extend lifespan and reduce mortality in patients with type 2 diabetes.
- It was once among the 8 "unrefusable" anti-aging drugs recommended by David Sinclair.
- This year, it achieved an astonishing 41.4% lifespan extension in a large number of non-human primates.
- New research this year confirms it can promote wound healing, improve cognitive function, inhibit atherosclerosis, and treat Alzheimer’s disease...
Figure Note: Key milestones in Metformin’s use for diabetes and age-related diseases (e.g., first approved for diabetes in France in 1957; approved in the U.S. in 1995; research on lifespan extension and cancer risk reduction).
Yes, it’s Metformin—the anti-aging substance that sparks heated discussions every time it’s mentioned, and one that instantly comes to mind!
Although it was not selected for the ITP program and the large-scale clinical trial TAME (Targeting Aging with Metformin) has yet to launch, these setbacks have not hindered Metformin’s progress. Whether facing doubts or support, every challenge has shaped its anti-aging journey. As the saying goes, "In adversity, we either sink or swim"—and so far, Metformin is swimming strongly!