What can we do about our aging process? This seemingly simple yet deceptive question has perplexed philosophers and scientists alike. Several theories of ageing have been proposed, but an integrative and cohesive understanding of the process of ageing has long remained elusive.
However, research in the last decade is beginning to uncover a more tangible and arguably more cohesive understanding of ageing mediated by the process of cellular senescence. This phenomenon limits the ability of somatic cell division in an organism and ultimately results in increased accumulation of ‘senescent cells’ in tissues and organs. These cells appear to be directly responsible for the increased predisposition of the elderly to several debilitating disorders thereby impacting the lifespan. More crucially, the cellular senescence-centric integrated view is becoming more relevant in the pathology of distinct age-related disorders (including diabetes and cancer) which thus can provide a single common target to disruptively change our therapeutic outlook.
People are exposed to nutritional factors even before birth, and these dietary nutritional elements are indispensable for subsequent maintenance, growth, and development. Being so intimately associated with life in general and health in particular, understanding whether and how these factors can impact the complex process of ageing itself is very pragmatic. This work focuses on primary dietary nutritional elements such as carbohydrates, proteins, and fats as well as secondary nutritional elements such as plant polyphenols and probiotic bacteria for their role in impacting ageing through the modulation of cellular senescence.
Diet is a pragmatic factor for modulating aging. This is attributed to dietary factors that can augment cellular stress response capacity and improve oxi-inflammatory homeostasis. As our cellular senescence-centric understanding of aging improves, development of a curated dietary regimen with anti-aging attributes is certainly not far-fetched.Rohit Sharma
Cellular senescence and ageing
At the fundamental level, cellular senescence is a stress response mechanism that protects our cells from a variety of stressors (Fig.1). This mechanism is very different from apoptosis as it promotes sustained survival of cells (as senescent cells). However, how cells decide between apoptosis and cellular senescence is yet ambiguous. Nonetheless, that cellular senescence might be associated with ageing was first realised when a progressive increase in the accumulation of senescent cells in various mammalian tissues and organs was observed.
Subsequent studies demonstrated that senescent cells may be causatively associated with multiple age-related disorders and impact longevity. Since then, a flurry of interest in identifying modulators of cellular senescence including natural compounds or drug repurposing has been documented. Recent clinical trials have also yielded exciting prospects since the reduction in tissue senescent cell burden can prevent multiple disease burdens.
Primary dietary elements and cellular senescence
Carbohydrates are primary dietary factors that are recognized for their critical role in organismal energy requirements. However, excess intake of carbohydrates (especially glucose and fructose) is often associated with conditions such as obesity and diabetes. Regardless, there is enough evidence suggesting beneficial effects of specific carbohydrates isolated from various edible plants or cellular metabolic sugars such as pyruvate in the modulation of cellular senescence.
Carbohydrate classes from diverse food sources have also been demonstrated to suppress premature cellular senescence and excessive inflammation during ageing in experimental animals by modulating nutrient signalling cellular pathways as well as by augmenting cellular functions such as autophagy. As a result, there is evidence that the consumption of certain carbohydrates (such as trehalose) may have lifespan-extending effects.
Similar to carbohydrates, dietary fat consumption is also heavily scrutinised in modern times due to its role in promoting obesity and cardiovascular diseases. However, this generic recognition is highly inaccurate as fats are critical for cellular functions and their role in modulating cellular senescence is diverse and emerging. In terms of ageing, most studies indicate that diets rich in omega-3 polyunsturated fatty acids suppress stress, inflammation, and senescence which ultimately enhances organismal longevity.
It is now becoming increasingly apparent that a balanced approach to dietary intake of carbohydrates and fats is far more pragmatic in improving health and longevity as opposed to extreme diets such as those low in sugars and fats. Further, the source of carbohydrates and fats in the diet is yet another crucial parameter to be considered, and there is an accumulating rationale that consumption of a plant-based diet can enhance longevity as opposed to an animal-based diet.
Proteins are significant players in regulating the process of cellular senescence. Consumption of a high protein-rich diet is demonstrated to increase senescence in experimental animals and also enhance all-cause mortality and cancer risk in a clinical study. Proteins are the workhorses of the cells, and thus maintenance of cellular protein homeostasis is a critical factor defining cellular health and stress. This also underscores the importance of acquiring adequate amino acids/proteins in diet. Overall, the role and relevance of these three primary dietary macronutrients, i.e., carbohydrates, protein, and fats in shaping the course of ageing and its outcomes have been scrutinised and forms a major part of developing diet-oriented anti-ageing strategies.
Secondary dietary factors and cellular senescence
Not only primary macronutrients, secondary nutrients present in diet such as plant polyphenols (abundantly present in fruits and vegetables) and probiotic bacteria (abundant in fermented foods) are also gaining particular attention as anti-aging agents. There is clinical evidence that regular consumption of polyphenols can augment cell stress response capacity and extend the lifespan. Interestingly, it is understood that the well-known long and healthy life of Japanese people is strongly associated with their robust daily intake of dietary polyphenols averaging nearly 4 times higher than those of the European population often resulting in significantly decreased all-cause mortality.
Animal studies have also demonstrated that chronic intake of polyphenols can prevent tissue stress that directly results in attenuated DNA damage and suppression of the onset of premature cellular senescence. Further, polyphenols are known to regulate the cellular ‘nutrient signalling pathways’ that impact cellular metabolism and functions.
Probiotic bacteria modulate several aspects of human health and their direct or indirect role in impacting human longevity is also emerging. The gut microbial profile is dubbed as a predictor of longevity, and its modulation has been correlated with improved markers of ageing. An association between probiotic bacteria and cellular senescence has been hypothesised. There is evidence that secretory metabolites of probiotic bacteria can confer health-beneficial attributes even during ageing in organs distal to the gut. All this indicates that the consumption of probiotic-rich natural fermented food products could be beneficial in alleviating ageing and related disorders.
Diet is central to our existence. Although no elusive ‘anti-ageing’ diet is still known, nonetheless, it is clear that consumption of a balanced diet is a prerequisite to a healthy and long life. Dietary factors (even sugars/fats), albeit at varied degrees, appear to play a vital role in managing cellular senescence and age-related disorders (Fig. 2).
Since organismal ageing begins in cells themselves, maintaining cellular stress response capacity vis-à-vis chronological ageing through dietary factors represents the central theme of nutrition-oriented modulation of biological ageing.
However, the relationship between diet and ageing is very intricate, and a better understanding of how nutrients (or their lack thereof) impact ageing is essential. This presents exciting prospects in developing curated dietary regimens that can promise the extension of human healthspan and lifespan.
Diwan, B., & Sharma, R. (2022). Nutritional components as mitigators of cellular senescence in organismal aging: A comprehensive review. Food Science and Biotechnology, 31(9), 1089-1109. https://doi.org/10.1080/02667363.2022.2155932