Six Proteins Scientists Are Targeting To Slow Aging

Aging is a complex process; however, recent research suggests it might not be entirely inevitable.

Scientists are studying proteins that influence how our cells age, repair themselves and maintain function over time. From enzymes that boost cellular energy to growth factors that support tissue repair, these proteins are offering new clues about how we might slow age-related decline.

Here are six proteins at the forefront of anti-aging research and the ways they could one day help us live healthier, longer lives.

1. Sirtuins

Sirtuins are enzymes that use NAD⁺ to regulate stress responses, DNA repair and energy balance in cells. They were first linked to lifespan extension in yeast and later in worms, flies and mice, where boosting sirtuin activity often delayed aging and improved health.

In mammals, specific sirtuins have been tied to key processes: SIRT1 supports metabolism and stress resistance, SIRT3 protects mitochondria and SIRT6 promotes DNA repair. Mice that lack SIRT6 age quickly and die young, while extra SIRT6 extends lifespan.

Research suggests sirtuins also mediate some of the benefits of calorie restriction, an established method for extending lifespan in animals.

Scientists are now testing ways to activate sirtuins in people. Compounds such as resveratrol, synthetic sirtuin-activating drugs and NAD⁺ boosters are being studied for their potential to protect muscle, heart, brain and metabolic health during aging.

2. Bcl-2 family

As we age, many cells enter a state called senescence – they stop dividing but remain active, often releasing inflammatory molecules that damage surrounding tissue. These “zombie cells” are difficult to eliminate because they activate survival pathways, including proteins from the Bcl-2 family, which protect them from self-destructing.

To counter this, scientists have developed drugs called senolytics that block Bcl-2 family proteins, forcing senescent cells to die. One of the most studied is navitoclax (ABT-263), which has shown strong results in clearing senescent cells in animal models of lung disease, heart disease and after radiation therapy. Clearing these cells often improves tissue function and can extend health span in mice.

However, navitoclax comes with risks: because Bcl-2 proteins are also important in healthy cells such as platelets, the drug can cause side effects, including low platelet counts (thrombocytopenia).

Researchers are now testing smarter strategies – nanoparticle delivery systems or combination treatments – to make Bcl-2 inhibitors more precise, killing only senescent cells while sparing healthy ones.

Early human trials with related senolytic combinations suggest real potential, but Bcl-2–based therapies remain mostly at the experimental stage.

If scientists can solve the safety challenges, targeting the Bcl-2 family could become a powerful way to clean up harmful senescent cells and slow age-related decline.

3. Klotho

Klotho is a transmembrane protein that also exists in a soluble form, acting like a hormone in the body.

It was first linked to aging when mice lacking it developed symptoms of premature aging, such as weak bones, hardened arteries and shortened lifespan. Higher levels of Klotho, by contrast, have been associated with longer life and better brain and kidney function in animals.

Research suggests that Klotho helps control oxidative stress, calcium balance and signaling pathways such as insulin and IGF-1, which are tied to aging. In mouse studies, an increase in Klotho extended lifespan by up to 30% and improved resistance to cognitive decline. Human studies have shown that people with naturally higher Klotho levels tend to have better memory and a lower risk of age-related diseases, although the effect is smaller than in lab animals.

Therapies being explored include gene therapy to boost Klotho, recombinant Klotho protein injections and drugs that stimulate its production. These approaches could one day support brain health, kidney function and cardiovascular resilience in older adults.

4. TERT and RAP1

TERT is the protein component of telomerase, the enzyme that rebuilds telomeres – the protective caps at chromosome ends. Proteins in the shelterin complex, such as RAP1, help regulate how telomerase interacts with telomeres and prevent unwanted DNA damage responses.

Telomeres shorten with every cell division, and once they reach a critical length, cells stop dividing and enter senescence. This shortening is one of the best-known markers of cellular aging.  Together, TERT and RAP1 help decide how long cells can keep dividing before entering senescence.

Using gene therapy to reactivate TERT in aged mice extended lifespan by up to 24% and improved fertility, brain size and insulin sensitivity.

However, telomerase is also active in many cancers, and uncontrolled activation could give tumor cells a survival advantage. In humans, shorter telomeres are linked with heart disease, diabetes and early aging, but clinical use of TERT-based therapies, such as TA-65, remains experimental.

Researchers are still trying to find ways to target TERT and its regulators, such as RAP1, using telomerase activators, gene therapy and small molecules, with the challenge of finding a therapeutic window that supports healthy aging, without feeding cancer growth.

5. HSP90

Proteostasis refers to the balance of making, folding and clearing proteins; it is the cell’s way of keeping proteins healthy and functional. When this balance breaks down, damaged proteins build up, driving diseases such as Alzheimer’s and Parkinson’s. Proteins known as molecular chaperones, including HSP90, help stabilize other proteins and prevent harmful misfolding.

In aging, HSP90 becomes less effective, and the cell’s quality control machinery struggles to keep up. Studies show that targeting HSP90 can shift this balance. Inhibitors of HSP90, such as geldanamycin derivatives, destabilize damaged or stress-dependent proteins, pushing unhealthy cells (including senescent ones) toward removal. In mouse models, HSP90 inhibition has reduced inflammation and improved resilience to stress-related injury.

Therapies could expand in two directions: boosting HSP90 to protect healthy cells or selectively blocking it to clear damaged or senescent cells. However, the challenge is specificity, since HSP90 supports many proteins, broad inhibition risks toxicity. New approaches such as nanoparticle delivery systems and targeted inhibitors are being explored to refine this strategy.

HSP90 inhibitors such as 17-AAG (tanespimycin) have been tested in cancer trials, showing that HSP90 can be targeted in humans; however, side effects limit broad use. For aging, trials haven’t advanced as far

6. GDF11

GDF11 is a growth factor in the TGF-β family that may slow age-related decline and support tissue repair.

It first grabbed attention in the 1950s as a “young blood” protein that reversed signs of aging in mice when scientists stitched old and young mice together in “parabiosis” experiments. The older animals showed signs of rejuvenation – better muscle, heart, brain and stem cell renewal.

In 2013–2014, a Harvard group reported that GDF11 levels fall with age in mice, and that injections reversed heart thickening, improved muscle function and boosted brain health.

However, results have varied; some studies found no benefit or harmful effects, such as muscle loss or early death, when doses were too high. Although the original Harvard group has refuted their results, reporting that the assays they used confused GDF11 with myostatin, which actually blocks muscle growth.

Current evidence supports the idea that GDF11 has benefits within a narrow “therapeutic window,” but overdosing may trigger weight loss and muscle problems. Researchers are now refining dosing and delivery to harness regenerative effects without harm.