By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Intermittent fasting and the biological clock: what we actually know
Intermittent fasting is one of the most talked-about topics in longevity medicine. The idea is almost too tempting: eat very little for a few days, in a planned way, and the body switches on its maintenance mechanisms. According to the hypothesis, those mechanisms may slow the pace of aging.
New studies point to a possible effect on metabolic health. They also show changes in markers used to estimate biological age. Still, the road from better blood tests to an actually longer life is a long one, and getting there will take long-term research.
Prof. Valter Longo directs the Longevity Institute at the University of Southern California and is one of the researchers most closely associated with the science of fasting. In an interview published in September 2026, he laid out a central idea. In his view, a fasting-mimicking diet may encourage cellular repair and reduce metabolic risk. It may also slow processes linked to aging. Longo spoke ahead of the 75th annual meeting of the British Society for Research on Ageing (BSRA), held in Oxford on September 9-11, 2026.
Your body knows when you eat
Food is much more than a source of calories. Proteins, amino acids and blood sugar also act as biological signals. They tell cells what to do right now: grow and build tissue, or switch into a mode of saving, maintenance and repair.
One of the key hubs in this system is the TOR pathway, a nutrient sensor that works inside the cell. When energy and amino acids are plentiful, the pathway promotes growth, ramping up protein production and cell division. Longo adds that high levels of certain amino acids activate the pathway and the downstream enzyme S6K, which, he says, speeds up aging processes. When food availability drops for a limited time, on the other hand, the pathway quiets down and other maintenance mechanisms take priority.
The balance between these two states matters for health. The body needs protein and growth pathways to maintain muscle, bone and the immune system. At the same time, it may benefit from defined periods of maintenance and repair.
The idea behind intermittent fasting
This is where the idea of intermittent fasting comes from: a limited, planned metabolic pause. During that window the body changes modes, from growth and storage to maintenance and repair. When the food supply falls, the body turns to its glycogen and fat stores and increases its production of ketone bodies. According to Longo, the body also uses glycerol to make its own glucose.
At the same time, autophagy may kick in. This is the cell’s internal recycling system, which breaks down damaged proteins and components and reuses their raw materials. Studies in cells and animals credit it with an important role in maintaining cell quality. Research in humans, however, is still developing. No one knows how many hours of fasting it takes to activate autophagy in each tissue, so it’s hard to claim that any particular number of hours guarantees a “cellular cleanup.”
The practical message is simple. Regular breaks between meals give the metabolic system time to rest. During that time, glucose and insulin levels fall and the body starts to draw on its energy stores.
A fasting-mimicking diet: five days a month
The program Longo studied is not a water fast. Nor is it a daily 16:8 fast, meaning 16 hours of fasting and eight hours of eating. It is a plant-based diet, low in calories and relatively low in protein, that lasts only five days, after which you return to your usual diet. The food provides little energy, but its composition produces a metabolic response that partly resembles fasting.
In the clinical study, participants completed one such cycle a month for three months. The researchers found reductions in weight and belly fat. They also documented a drop in liver fat and, in a small subgroup, improved insulin resistance. In addition, the ratio of immune cells shifted toward a younger profile.
The finding that drew the most attention concerned biological age. The study, published in Nature Communications, found a median reduction of about 2.5 years in calculated biological age among the 52 participants. The reduction remained significant even after adjusting for weight change, so the researchers concluded that the effect was not due to weight loss alone. What’s more, a second clinical trial showed a median reduction of 2.7 years.
What actually dropped by two and a half years?
The researchers calculated biological age from seven measures: albumin, alkaline phosphatase, creatinine and C-reactive protein (CRP), plus glycated hemoglobin (HbA1c), systolic blood pressure and total cholesterol. In other words, this is a statistical estimate linked to the risk of illness and death. It is not a direct measurement of cellular age, nor is it an epigenetic clock.
Put differently, the participants’ metabolic and inflammatory profile improved and came to resemble that of a younger, healthy person. The study does not prove that they became two and a half years younger, nor that their lives will be longer. The life-expectancy projections in the paper are based on statistical modeling, not on actual mortality follow-up. Even so, improvements in blood pressure, blood sugar, liver fat and inflammation may add years of healthy life. In this context, it is also worth reading about weight-loss drugs and biological age.
Intermittent fasting: the greatest potential is in those who need it most
The effect was especially pronounced in participants at risk: those with excess weight, high blood pressure, high glucose or elevated inflammatory markers. In this group, calculated biological age fell from 43.3 to 40.4 years after three cycles. The finding fits a well-known principle of preventive medicine: the higher the risk at the start, the more room there is for improvement.
Individual responses also varied. In 16 of the 52 participants, about 31%, calculated biological age actually went up. For comparison, in the control group it rose in 12 of 19 participants. So intermittent fasting does not promise the same effect for everyone.
A moderate overnight fast may be enough
For everyday life, Longo suggests a simple alternative: an eating window of about 12 hours alongside an overnight fast of about 12 hours. For example, finish dinner by 7 p.m. and eat breakfast after 7 a.m. In his view, a window like this is easy to follow and safe, and it is less likely to cause muscle loss than a daily 16-hour fast.
This approach cuts down on late-night eating and works with the body’s internal clock. It also leaves room to spread enough protein across the day. I have written more about this in my articles on meal timing and longevity and on sleep and night eating.
What the research says about an early eating window
Controlled studies show that time-restricted eating can improve weight and metabolic measures. In general, a window in the morning and early afternoon works better than a late one. For example, a 2026 network meta-analysis included 39 randomized trials and 3,236 participants. Most approaches reduced body measurements compared with controls, and an early eating window lowered fasting glucose and insulin resistance. However, the researchers rated the certainty of the evidence as very low to moderate for most outcomes. Another review in BMJ Medicine likewise found only a modest effect of an early window on fasting blood sugar.
On the other hand, in 2024 a report at an American Heart Association conference described higher cardiovascular mortality among people who ate within a window shorter than eight hours. The finding came from an observational study based on only two dietary reports. It was presented as an abstract, without full peer review, and showed only a statistical association, not cause and effect. All in all, the data support a balanced, personalized approach.
Muscle remains a central part of the equation
Lengthening your fasting hours can shrink the opportunities to eat enough protein and energy. This matters especially in older age and during weight loss. It also matters during treatment with weight-loss medications and for people with low muscle mass.
The goal in longevity medicine is clear: improve metabolic health while preserving muscle, strength and function. That’s why any intermittent fasting plan should include adequate protein intake. It’s also wise to add strength training two to three times a week and to avoid losing weight too quickly. Sometimes protecting your muscle matters more than one more hour of fasting. Read more about this in my article on how to prevent muscle loss during weight loss.
Who intermittent fasting is not right for
Some groups need a different approach: pregnant or breastfeeding women, children and teenagers, and people who are underweight. The same applies to people dealing with eating disorders, frailty, sarcopenia or serious chronic illness. In addition, people treated with insulin or other drugs that can lower blood sugar need particular caution. For them, any change in meal timing should be medically supervised.
The bottom line: a smart pause, not a chase after hunger
The science around intermittent fasting points in an intriguing direction. When we eat matters, not just how much and what. Short, planned periods of dietary restriction may improve metabolic markers and activate repair mechanisms. The practical path starts with moderate steps:
- Eat dinner earlier and cut back on late-night snacking.
- Keep an overnight fast of about 12 hours and follow a high-quality Mediterranean diet.
- Eat enough protein and include activity that preserves muscle.
The chronological clock keeps ticking at a steady pace. But our everyday choices may influence the pace at which the body ages and functions. That is the very heart of longevity medicine.
The information in this article is general and does not replace personal medical advice.
References
Aging expert: How intermittent fasting could turn back the biological clock
8-hour time-restricted eating linked to a 91% higher risk of cardiovascular death
