A major 2023 study has reported ‘acting on diet is one of the most accessible ways to intervene in human ageing’.

A team of European researchers has identified 12 key indicators ‘which are measurable processes that change with the ageing of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of ageing’.

The authors note ‘each of these indicators should be considered an entry point for future exploration of the ageing process, as well as for the development of new anti-ageing drugs’.

Assessing the new study Dr Javier Gomez Pavon, from the leadership team at the Spanish Society of Geriatrics and Gerontology, told Medscape.com this research confirmed ‘diet is currently the most easily accessible form of intervention to slow down ageing’.

The collaborative study titled ‘Hallmarks of Ageing: An expanding universe’ – by scientists from research institutions in Spain (Spanish National Cancer Centre, University of Oviedo, and Barcelona Institute of Science and Technology), England (University College London), Germany (Max Planck Institute for Biology of Ageing) and France (University of Paris) – has been published in the international journal Cell.

In their study, the researchers propose the following 12 hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis.

The researchers explain that ageing is driven by hallmarks fulfilling three premises:

  • their age-associated manifestation;
  • the acceleration of ageing by experimentally accentuating them; and
  • the opportunity to decelerate, stop or reverse ageing by therapeutic interventions on them.

These hallmarks ‘are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organisational features of spatial compartmentalisation, maintenance of homeostasis, and adequate responses to stress’.

Molecular indicators of ageing in mammals

An earlier 2013 study, also published in Cell, summarised for the first time nine molecular indicators of ageing in mammals – and served as an important ‘knowledge map about ageing’.

Since then ‘a barometer on interest in the topic is that approximately 300,00 articles on ageing have been published’, noted Medscape.com – which is ‘as many as were published during the previous century’.

In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm interventions in the ageing process can prevent, delay, and even avoid age-related diseases such as cancer.

With publication of the team’s new updated 2023 study, ‘spectacular progress is being made in slowing down ageing’, commented Medscape.com, ‘with three new molecular indicators of measurable and manageable processes that accelerate or slow down deterioration associated with age, as well as age-related pathologies’.

And most importantly: ‘These findings are closer than ever to being applied in older adults.’

Study co-author Dr Maria Blasco, scientific director at Spain’s National Cancer Research Centre and an international leader in telomere research, noted on the NCRC website: ‘The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human ageing.’

The new study includes a table listing 80 recent ‘experimental interventions’ with mammals (mostly mice) which suggest it is possible to prolong life or treat age-associated diseases.

Some of those studies involve humans; others specifically investigate how to delay ageing through diet.

The study’s authors emphasise: ‘Acting on the diet is one of the most accessible ways to intervene in human ageing.’

Following the 80 ‘experimental interventions’ since the initial 2013 research, and now the latest study verifying and expanding the conclusions of that analysis a decade ago, Dr Blasco summed up: ‘Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases.’

A table full of fruit and vegetables

Molecular signatures ‘indicators of ageing’

In the new study, the researchers have identified their 12 indicators of ageing: molecular signatures which mark the progress of a particular process – and on which it was possible to act to prolong life.

In addition, they highlight four primary causes of ageing: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation.

These are strongly inter-connected processes and ageing results from their joint action – potentially providing multiple ways to act on the physiologic process of ageing.

And currently, diet is the most accessible form of intervention.

Dietary interventions are related to a key indicator of ageing: the dysregulation of the ‘nutrient sensing mechanism’ – the network of molecular signals that alert all mammals that food is available.

The researchers noted: ‘Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions.

‘However the results obtained in this line in our species are still unclear; clinical trials based on dietary restrictions in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation.’

Low disease diets

Dr Javier Gomez Pavon from the Spanish Society of Geriatrics and Gerontology noted current evidence indicates certain types of ‘diet in population cohort’ studies are associated with a lower incidence and prevalence of certain diseases.

Among many contrasting examples he cited:

  • the Mediterranean diet has been shown to be associated
  • with lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and lower risk of cognitive impairment, especially due to its vascular component;
  • eating nuts (almonds, walnuts) is associated with less dyslipidemia;
  • a diet rich in fibre is also associated with less colonic digestive pathology, such as constipation and especially colon cancer;
  • a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast and colon disease;
  • a diet with adequate protein intake is related to better muscle mass at all ages;
  • a diet rich in calcium products (nuts and dairy products) is linked to better bone mass and less osteoporosis.

Dr Pavon observed: ‘At the moment, there is no study that links any type of diet with greater longevity – although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, and avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free ageing.’

Common dietary myths

Since diet is currently the ‘most easily accessible element to slow down ageing’, Dr Pavon told Medscape.com it is important to refute many widespread myths currently circulating about food and longevity.

One myth regarding dairy products is that yoghurt is not useful for the elderly because they do not have adequate enzymes to digest it, and it is only for children or young people who are growing.

Dr Pavon retorted: ‘It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content – fundamental elements at all ages, but especially in ageing, where there is bone loss secondary to ageing itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.’

Another common myth it that ‘it is not good to eat fruit with meals’.

Dr Pavon answered: ‘Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits) are undoubtedly the most important components against pathological ageing (stroke, myocardial infarction, dementia).

‘It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.’

A further common myth is the ‘fact’ that ‘sugars in legumes and bread are harmful’. Dr Pavon answered: ‘Again it is not true. In addition to sugar, legumes contain fibre and other very important antioxidants, just like bread. The difference is the amount, as in all food.

‘On the contrary, refined sugars, such as pastries, sugary drinks, etc, should be avoided, since they are directly related to cardiovascular disease and obesity.’

Dr Pavon also commented: ‘As for the popular saying ‘Do not even try meat’, it is not sound since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron, and therefore are necessary.

‘As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol.’

Dr Pavon also cautioned about wine consumption, noting: ‘Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power; but at more than these amounts, the negative power of alcohol predominates over its benefits.’

Ageing indicator ‘entry points’

The new European study expands the previous study’s list of accepted ageing indicators from nine to 12 ‘measurable processes that change with the ageing of the organism’ – and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption or even a regression of ageing.

The authors concluded: ‘Each of these indicators should be considered an entry point for future exploration of the ageing process’.

Co-author Dr Blasco explained that, where a decade ago it was recognised telomere shortening was at the origin of age-related diseases, ‘it is now emphasised that the generation of mouse models with short telomeres has shown telomeric wasting is at the origin of prevalent age- associated diseases, such as pulmonary and renal fibrosis.’

The 2023 study reviews new interventions to delay ageing and age-related diseases to act on telomeres.

Dr Blasco said: ‘For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia.’ CBM