bims-minfam 2023-07-23 papers

Issue of 2023–07–23
eight papers selected by
Ayesh Seneviratne, Western University

Nutr Res Rev. 2023 Jul 20. 1-27

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.

So-Hyun Park, Da-Hye Lee, Dae-Hee Lee, Chang Hwa Jung.

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or "healthspan," has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when, and how much one eats. Dietary restriction, including calorie restriction, fasting, or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

Keywords: aging; healthspan; lifespan extension; phytochemicals

DOI: https://doi.org/10.1017/S0954422423000136

Front Aging. 2023 ;4 1199596

Frontiers in aging special issue: DNA repair and interventions in aging perspective on "loss of epigenetic information as a cause of mammalian aging".

Ethan D Schaffer, Isabel Beerman, Rafael de Cabo, Robert M Brosh.

The recently published article in Cell by the Sinclair lab and collaborators entitled "Loss of Epigenetic Information as a Cause of Mammalian Aging" [1] implicates heritable changes in gene expression as the basis for aging, a postulate consistent with the emerging information theory of aging. Sinclair's group and colleagues induced epigenetic changes, i.e., DNA and histone modifications, via double-strand breaks (DSBs) catalyzed by the I-Pol endonuclease at specific genomic loci. The genomic DNA breaks, introduced without inducing insertion or deletion mutations (indels) in a mouse model, were targeted to 19 non-coding regions and one region in ribosomal DNA (rDNA), the latter shown to not have a significant effect on the function or transcription of rDNA [1]. With that experimental model in place, the authors present experimental evidence supporting a model that epigenetic changes drive aging via this inducible DNA break mechanism. After demonstrating the phenotypic alterations of this accelerated aging, they attempt to reverse selective phenotypes by resetting the altered epigenetic landscape. Establishing a causal relationship between epigenetic changes and aging, and how this connection might be manipulated to overturn cellular features of aging, is provocative and merits further study.

Keywords: DNA damage; aging; double-strand break; epigenetic; gene expression; genetic; healthspan; mouse

DOI: https://doi.org/10.3389/fragi.2023.1199596

Aging (Albany NY). 2023 Jul 20. 15

Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?

Mikhail V Blagosklonny.

Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.

Keywords: Alzheimer’s disease; cancer; health span; hyperfunction; lifespan; mTOR

DOI: https://doi.org/10.18632/aging.204920

Age Ageing. 2023 Jul 01. pii: afad127. [Epub ahead of print]52(7):

New Horizons in cellular senescence for clinicians.

Miles D Witham, Antoneta Granic, Satomi Miwa, Joao F Passos, Gavin D Richardson, Avan A Sayer.

Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state-the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.

Keywords: cellular senescence; human ageing; interventions; older people; senescence-associated secretory phenotype; senolytics; senotherapeutics

DOI: https://doi.org/10.1093/ageing/afad127

Nat Med. 2023 07;29(7): 1623-1630

Digital health for aging populations.

Chuanrui Chen, Shichao Ding, Joseph Wang.

Growing life expectancy poses important societal challenges, placing an increasing burden on ever more strained health systems. Digital technologies offer tremendous potential for shifting from traditional medical routines to remote medicine and transforming our ability to manage health and independence in aging populations. In this Perspective, we summarize the current progress toward, and challenges and future opportunities of, harnessing digital technologies for effective geriatric care. Special attention is given to the role of wearables in assisting older adults to monitor their health and maintain independence at home. Challenges to the widespread future use of digital technologies in this population will be discussed, along with a vision for how such technologies will shape the future of healthy aging.

DOI: https://doi.org/10.1038/s41591-023-02391-8

Cancer Drug Resist. 2023 ;6(2): 273-283

Mitochondria in colorectal cancer stem cells - a target in drug resistance.

Mateus de Almeida Rainho, Priscyanne Barreto Siqueira, Ísis Salviano Soares de Amorim, Andre Luiz Mencalha, Alessandra Alves Thole.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second most deadly type of cancer worldwide. In late diagnosis, CRC can resist therapy regimens in which cancer stem cells (CSCs) are intimately related. CSCs are a subpopulation of tumor cells responsible for tumor initiation and maintenance, metastasis, and resistance to conventional treatments. In this scenario, colorectal cancer stem cells (CCSCs) are considered an important key for therapeutic failure and resistance. In its turn, mitochondria is an organelle involved in many mechanisms in cancer, including chemoresistance of cytotoxic drugs due to alterations in mitochondrial metabolism, apoptosis, dynamics, and mitophagy. Therefore, it is crucial to understand the mitochondrial role in CCSCs regarding CRC drug resistance. It has been shown that enhanced anti-apoptotic protein expression, mitophagy rate, and addiction to oxidative phosphorylation are the major strategies developed by CCSCs to avoid drug insults. Thus, new mitochondria-targeted drug approaches must be explored to mitigate CRC chemoresistance via the ablation of CCSCs.

Keywords: Cancer stem cells; colorectal cancer; drug resistance; mitochondria; mitophagy

DOI: https://doi.org/10.20517/cdr.2022.116