Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors.

Gelotology (the study of laughter) has it seems mainly evaded the attention of longevity scientists, positive biologists, and geroscientists. However, the potential of laughter to result in immediate improved affect, increase overall well-being, reduce cortisol levels, benefit the immune system, and support cardiovascular health, to name only a few of its possible effects, renders it of high interest as an anti-aging strategy. As an intervention, laughter has, at least theoretically, the potential to slow the process of aging, and to ameliorate its lived experience. What makes laughter particularly attractive is that it is accessible to all, is very low risk, and is inherently, for most people, enjoyable. Ten years ago, lifestyle medics first proposed that laughter be prescribed in primary care. They pointed to its efficacy in general patient care, geriatrics, rheumatology, critical care, oncology, rehabilitation, psychiatry, home care, palliative care, terminal care, and hospice care. Nevertheless, laughter prescription has been slow to take off. It is therefore of interest to contemplate why, how, and to what effect, laughter can be harnessed to improve people’s lives. Quality research is recommended to uncover the secrets of laughter, its dynamic effects on the body, if, and how, it may impact longevity, and how it can best be used to promote successful and active aging.

Progeroid syndromes are characterized by clinical signs of premature ageing, which may contain several diseases such as Werner syndrome, Bloom syndrome, Rothmund-Thomson syndrome, Hutchinson-Gilford progeria syndrome, and Cockayne syndrome. These disorders may also exhibit some pathological involvements reminiscent of primary mitochondrial diseases. Emerging evidence has linked mitochondria even to physiological ageing. In addition, alterations in the maintenance pathway of mitochondria have been also deliberated as relevant in age-related diseases. In particular, mitophagy and its regulatory pathway might be key process for the homeostasis of mitochondria. Therefore, chronic DNA damage and/or the activation of poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) could be a threat to the mitochondrial alterations. The PARP1 is an enzyme responding to the DNA damage, which might be also involved in the mitophagy. Interestingly, the PARP1 has been reported to play an important role in the longevity of lifespan, which has attracted growing attention with the social development. This review may provide a rationalized overview of the involvement of mitochondrial oxidative stresses in genetically defined accelerated ageing, progeroid syndromes, physiological ageing, and/or age-related diseases for the innovative therapeutic approaches.

The paper aims to review the possibilities of a complex transdisciplinary approach to forming health and longevity. Determinants of productive longevity (DPL) and health culture are reviewed; definitions of health, stress, and eustress, and their roles in active and productive longevity are given. DPL making a decisive contribution to the phenomenon of active longevity are stated and analyzed from the point of view of evidence-based medicine. They are as follows: 1) environmental factors including geographical location, “Blue zones”, and mountain areas, as well as level of the environmental pollution; 2) dietary regimen to support active longevity, including vegetarianism, calorie restriction, fasting, the role of vitamins, biological antioxidants, geroprotectors, and micronutrients; 3) importance of activity and eustress phenomenon, by other words, lifestyle: physical activity, sexual relationship, Qigong and Yoga practices, cognitive activity, sense of humor, and acceptance of age in activities of daily living and survival; 4) genetic and epigenetic particularities as a condition for long-living; 5) level of health care and early diagnostics to prevent age-associated diseases; 6) the role of the state of mind and meditation as well, how it is used for forming health due to Qigong and Yoga natural systems, in religion, and medical practice; 7) motivation for active longevity that significantly increases chances to productive longevity.

Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases.