Spectacular progress is being made in slowing down aging, 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. These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.

An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.

A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, 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 that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.

María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and co-author of the study, noted on the institution’s 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 aging.”

Eighty Experimental Interventions

The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Blasco. The researchers identified nine indicators of aging ― molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.

They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.

Nutrient Sensors

Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.

“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 restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” write the researchers.

Diet and Disease

Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told Medscape Spanish Edition, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”

Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”

Eating nuts (eg, almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, 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, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.

“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, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Gómez.

Aging Indicators

The article expands the aging indicators from nine to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.

“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers conclude.

A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.“

The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Blasco added.

Food Fact and Fiction

Since diet is currently the most easily accessible element to slow down aging, Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes for to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging 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 myth is that it is not good to eat fruit with meals. “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, etc) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc). 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.”

Sugars and Meat

“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber 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,” added Gómez.

“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,” added Gómez.

Another phrase that circulates around is that wine is food. “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,” concluded Gómez.

This article was translated from the Medscape Spanish edition.