Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members
of its kind in histone deacetylase family in governing multiple cellular fates, is
predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner
to inhibit transcription activity of p53, in turn modulate pathways that are implicated
in regulation of tissue homoeostasis and many disease states. In this review, we discuss
the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which
are implicated in cellular aging, cancer and reprogramming. It is noteworthy that
these cellular events share few common regulatory pathways, including SIRT1-p53-LDHA-Myc,
miR-34a,-Let7 regulatory network, which forms a positive feedback loop that controls
cell cycle, metabolism, proliferation, differentiation, epigenetics and many others.
In the context of aging, SIRT1 expression is reduced as a protective mechanism against
oncogenesis and for maintenance of tissue homeostasis. Interestingly, its activation
in aged cells is evidenced in response to DNA damage to protect the cells from p53-dependent
apoptosis or senescence, predispose these cells to neoplastic transformation. Importantly,
the dual roles of SIRT1-p53 axis in aging and tumourigenesis, either as tumour suppressor
or tumour promoter are determined by SIRT1 localisation and type of cells. Conceptualising
the distinct similarity between tumorigenesis and cellular reprogramming, this review
provides a perspective discussion on involvement of SIRT1 in improving efficiency
in the induction and maintenance of pluripotent state. Further research in understanding
the role of SIRT1-p53 pathway and their associated regulators and strategies to manipulate
this regulatory axis very likely foster the development of therapeutics and strategies
for treating cancer and aging-associated degenerative diseases.