The latest in anti-aging: Can a calorie deficit extend your lifespan?

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Fact-checked by Barbara Bekiesz
Published February 13, 2024

Key Takeaways

  • Calorie restriction (CR) without malnutrition has proven to be one of the most effective non-drug approaches for extending lifespan and improving health.

  • CR reduces the risk of cardiovascular diseases by reversing cell damage, oxidative stress, and nutrient signaling pathway dysfunction.

  • Other therapeutic strategies to promote healthy aging include senolytics, metformin, NAD boosters, resveratrol, rapamycin, and taurine.

Restricting calorie intake below what's needed for weight maintenance has been a vital health discovery of the 20th century.

Multiple studies have shown this restriction delays primary aging (related to our natural cell and tissue deterioration rate) and secondary aging (influenced by lifestyle and comorbidities) in various organisms.

Benefits of caloric deficit

A caloric restriction (CR) involves consuming fewer calories without specific restrictions. This involves a decrease in energy intake, with a considerable drop in calories, often by 10% or more in human research, according to a review article on CR published in the Journal of Cardiopulmonary Rehabilitation and Prevention.[]

Recent studies have provided evidence of CR's positive effects on human health, showing weight loss and improved physiological markers in both short and long-term CR trials. As discussed in an article in Aging Research Reviews, CR delays cardiovascular aging and reduces the risk of atherosclerotic cardiovascular disease (CVD).[] Various populations, like residents of Okinawa Island (Japan), Biosphere 2 researchers, and Calorie Restriction Society International members, experience improved physiological functioning due to CR.

Let's take a closer look at the data:

  • The CALERIE phase 2 study followed 220 non-obese participants for 2 years who achieved an average 11.7% calorie reduction vs controls. The research showed reductions in resting metabolic rate, total energy expenditure, triiodothyronine, leptin, and oxidative stress markers.[]  

  • CR led to significant and lasting improvements in CVD risk factors, including lipid profile, blood pressure, glucose tolerance, and insulin sensitivity.

  • Additionally, the CR group experienced potential anti-aging benefits, like improvements in body composition, cardiometabolic risk markers, markers of inflammation, and aerobic fitness, without any negative impact on psychological and behavioral factors.

  • Earlier studies indicated that even 10 weeks of CR interventions reduced hypertension, resting metabolic rate, and blood glucose levels. 

Similar data previously emerged from the animal kingdom, where a 20-year study on rhesus macaques at the Wisconsin National Primate Research Center found that calorie restriction led to a lower incidence of aging-related deaths, including those attributed to diabetes, cancer, CVD, and brain atrophy.[]


Decades of research in diverse organisms, from yeast to non-human primates, reveals CR’s significant impact on aging and longevity, extending maximal lifespan by up to 60%. The authors of the CR review article explain that the mechanisms for this effect include increased apoptosis, decreased oxidative damage, lower body temperature, and normalization of the nutrient signaling pathway. These processes collectively contribute to its life-prolonging effects, involving the reduction of free radicals and the concept of "hormesis."

The hormesis concept postulates that exposure to low levels of stress or toxins can activate the body's adaptive responses, making it stronger and more resilient. Restricted calorie consumption can stress the body’s metabolism and prompt adaptive mechanisms, such as improved energy efficiency, better fat utilization, and increased cellular repair. 

Alternatives to conventional CR diets

Despite its touted benefits, conventional daily CR can be tough to stick to long-term, thanks to the easy availability of energy-rich foods and drinks. The authors writing in Aging Research Reviews state that an established alternative is intermittent fasting (IF), involving adjusted meal timing and extended energy restriction, often for 12 hours.

Another emerging approach is protein restriction, whereby daily protein intake is limited to 10% or less of energy supply. This potentially slows mammalian aging by inhibiting the growth hormone IGF-1 axis.

Other therapies that enhance longevity

Senolytics, such as dasatinib, quercetin, and UBX1325, have demonstrated encouraging outcomes in laboratory trials by eliminating senescent cells and diminishing inflammation.

Related: How to protect your youthful glow against ‘inflammaging’

Several other drugs and supplements may impact the aging process through mechanisms related to cellular rejuvenation.[]

Metformin, a drug used to treat type 2 diabetes, supports metabolic rejuvenation by AMPK activation. It also combats inflammatory damage and dysfunction in neural cells and enhances remyelination. Metformin's direct mTORC1 inhibition renews stem cells and counters age-related traits. 

Taking nicotinamide supplements boosts the body's NAD+ levels, which in turn increases the activity of SIRT1, leading to better blood vessel function and reversing age-related issues by decreasing oxidative stress.

Resveratrol, an antioxidant found naturally in red grapes and berries, helps in the cellular rejuvenation of the aging heart. It upregulates cardioprotective genes, antioxidants, and heat shock proteins.

Rapamycin, like CR, hinders the mTOR pathway, slowing cell growth and extending lifespan. But its side effects, like anemia and insulin issues, restrict its use. Scientists are now seeking "rapalogs" mimicking the benefits without these problems.

In addition, taurine, an amino acid commonly used as a dietary supplement, has been shown to reduce mitochondrial dysfunction. Research supports its role in delaying the onset of aging.[] 

While these therapies show potential, their usage is still experimental. Clinical trials exploring their potential in preventing CVD, cognitive decline, and cancer are underway.

What this means for you

Apart from recommending calorie restriction to your patients as an approach to improve their health and longevity, you can advise them to adopt a diet rich in colorful fruits and vegetables, known as "eating the rainbow." Leafy greens, whole fruits (not juice), and legumes should be part of this diet. Additionally, choosing whole grains over refined grains supports healthy weight management and reduces cholesterol absorption, ultimately lowering the risk of CVD and premature aging.

Read Next: What precision nutrition can do for your patients
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